# NM_001271696.3(ABCB7):c.1158T>C (p.Ser386=)

https://sugi.bio/variant/abcb7-p-ser386

## Summary

**ABCB7 p.Ser386= (c.1158T>C)** is classified **Likely benign** in ABCB7 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). Very rare (popmax 0.00658%, amr).

**At a glance:** Likely benign · review: Single submitter · rsID rs1268328600 · 1 submitter · very rare (popmax 0.00658%, amr)

## For patients & families {#patients}

This is a change in the ABCB7 gene that is classified as likely benign — not considered disease-causing, submitted by 1 submitter.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

**Support & next steps:** [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [ABCB7](https://sugi.bio/atlas/gene/ABCB7/) |
| Protein change (HGVS p.) | p.Ser386= |
| Coding change (HGVS c.) | c.1158T>C |
| MANE Select transcript | [NM_001271696](https://www.ncbi.nlm.nih.gov/nuccore/NM_001271696) |
| dbSNP | [rs1268328600](https://www.ncbi.nlm.nih.gov/snp/rs1268328600/) |
| Variant type | single nucleotide variant |
| Location | chrX:75071558-75071558 (GRCh38) |
| ClinVar | [VCV755891](https://www.ncbi.nlm.nih.gov/clinvar/variation/755891/) |

**All HGVS expressions:** `LRG_1162:g.89726T>C`, `LRG_1162t1:c.1161T>C`, `LRG_1162t2:c.1158T>C`, `NC_000023.10:g.74291393A>G`, `NC_000023.11:g.75071558A>G`, `NG_007980.3:g.89726T>C`, `NM_001271696.3:c.1158T>C`, `NM_001271697.3:c.1038T>C`, `NM_001271698.3:c.1080T>C`, `NM_001271699.3:c.1041T>C`, `NM_004299.6:c.1161T>C`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation and, for splice-region changes, SpliceAI (below), not from a missing predictor score.
- SpliceAI predicts **donor gain** (Δ 0.25) — a splice-altering prediction the current classification does not reflect
- Conservation: phyloP 2.942, GERP -2.57, phastCons 0.988 — highly conserved position (PP3-type support)
- CADD: **PHRED 9.186**. No single ClinGen-calibrated threshold exists and the expert panels that use CADD disagree — GUCY2D/AIPL1 require ≥ 20.0 for an untranslated-region variant, ABCA4 ≥ 28.1 for a synonymous or indel variant, the Pulmonary Hypertension panel imports Pejaver 2022's missense-calibrated numbers, and the Antibody Deficiencies panel declines CADD entirely for PIK3CD. CADD v1.7 also incorporates Zoonomia phyloP, so it partly re-expresses the conservation above. *Descriptive; no threshold applied.*
- SpliceAI deltas (raw): acceptor loss **0.00**, donor loss **0.00**, acceptor gain **0.00**, donor gain **0.25**. Largest is donor gain.
- SpliceAI deltas (masked): acceptor loss **0.00**, donor loss **0.00**, acceptor gain **0.00**, donor gain **0.25**.
- Population frequency (gnomAD v4.1): grpmax **0.00658%** (amr) · FAF95 0.00174% · FAF99 0.000883% · 3/45,623 in the highest group · 4/1,209,483 alleles overall — very rare (popmax 0.00658%, amr).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| Admixed American (grpmax) | 0.00658% | 15,208 |
| European (non-Finnish) | 0.000112% | 895,063 |

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Gene constraint & dosage {#gene-context}


Curated gene–disease validity (ClinGen):

- **mitochondrial disease** — Moderate (XL)

## Protein context {#protein}

Residue **386** lies in the abc transmembrane type-1 domain; an α-helix.

AlphaFold model confidence (whole protein): pLDDT 78.19, 48% of residues very-high.

**4 experimental structure(s)** (PDB): [23PG](https://www.rcsb.org/structure/23PG), [23PH](https://www.rcsb.org/structure/23PH), [23PI](https://www.rcsb.org/structure/23PI), [7VGF](https://www.rcsb.org/structure/7VGF).

## What this gene does {#gene-function}

*Describes the biological roles of ABCB7 (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** ABCB7's established molecular role includes identical protein binding. p.Ser386= falls in the abc transmembrane type-1 domain.


### Pathways affected {#pathways}

ABCB7 participates in **2 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [Mitochondrial ABC transporters](https://reactome.org/content/detail/R-HSA-1369007) | curated |
| [Cytosolic iron-sulfur cluster assembly](https://reactome.org/content/detail/R-HSA-2564830) | electronic |

### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** identical protein binding, protein homodimerization activity, ABC-type iron-sulfur cluster transporter activity.

**Biological process:** intracellular iron ion homeostasis, iron ion transmembrane transport, positive regulation of heme biosynthetic process, iron-sulfur cluster export from the mitochondrion, positive regulation of iron-sulfur cluster assembly.

## Clinical significance {#significance}

**Likely benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2019-12-31.

**Submitter consensus:** unanimous (1/1 Likely benign).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Likely benign | criteria provided, single submitter | clinical testing | 2019-12-31 |

**Reported phenotype names (ClinVar):** not provided, RECLASSIFIED - ADRA2C POLYMORPHISM, RECLASSIFIED - ADRB1 POLYMORPHISM, none provided.

## Similar variants {#similar}

Related ABCB7 variant pages (same residue, condition, or type): [ABCB7 c.1659+5T>G](/variant/abcb7-c-1659-plus-5t-g), [ABCB7 c.1935+5G>C](/variant/abcb7-c-1935-plus-5g-c), [ABCB7 p.Ala5Glu](/variant/abcb7-p-ala5glu), [ABCB7 p.Arg711His](/variant/abcb7-p-arg711his), [ABCB7 p.Asn378Asp](/variant/abcb7-p-asn378asp), [ABCB7 p.Asp653Asn](/variant/abcb7-p-asp653asn), [ABCB7 p.Glu494Gln](/variant/abcb7-p-glu494gln), [ABCB7 p.Gly197Cys](/variant/abcb7-p-gly197cys).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-11); gnomAD v4.1 (Broad Institute, built 2026-10-06); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-07-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 755891). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*