# NM_022437.3(ABCG8):c.15G>C (p.Ala5=)

https://sugi.bio/variant/abcg8-p-ala5

## Summary

**ABCG8 p.Ala5= (c.15G>C)** is classified **Likely benign** in ABCG8 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-05-13). Very rare (popmax 8.72e-05%, nfe).

**At a glance:** Likely benign · review: Single submitter · rsID rs200951677 · 1 submitter · very rare (popmax 8.72e-05%, nfe)

## For patients & families {#patients}

This is a change in the ABCG8 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 | [ABCG8](https://sugi.bio/atlas/gene/ABCG8/) |
| Protein change (HGVS p.) | p.Ala5= |
| Coding change (HGVS c.) | c.15G>C |
| MANE Select transcript | [NM_022436](https://www.ncbi.nlm.nih.gov/nuccore/NM_022436) (variant reported on NM_022437) |
| dbSNP | [rs200951677](https://www.ncbi.nlm.nih.gov/snp/rs200951677/) |
| Variant type | single nucleotide variant |
| Location | chr2:43839068-43839068 (GRCh38) |
| ClinVar | [VCV1096144](https://www.ncbi.nlm.nih.gov/clinvar/variation/1096144/) |

**All HGVS expressions:** `LRG_1181:g.4752C>G`, `LRG_1182:g.12127G>C`, `LRG_1182t1:c.15G>C`, `NC_000002.11:g.44066207G>C`, `NC_000002.12:g.43839068G>C`, `NG_008883.1:g.4752C>G`, `NG_008884.2:g.12127G>C`, `NM_001357321.2:c.15G>C`, `NM_022437.3:c.15G>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 (below), not from a missing predictor score.
- Conservation: phyloP -0.648, GERP -2.27 — not a conserved position (phyloP < 0.1, ACGS BP7 cut)
- CADD: **PHRED 1.677**. 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: **not looked up on this page** — it was served without the gene's SpliceAI index, so no lookup was made. This is a gap in this page, not in the data, and says nothing about whether a splicing effect is predicted.
- Population frequency (gnomAD v4.1): grpmax **8.72e-05%** (nfe) · 1/1,146,802 in the highest group · 1/1,398,762 alleles overall — very rare (popmax 8.72e-05%, nfe).

*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.*

## Clinical significance {#significance}

**Likely benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2020-05-13.

**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 | 2020-05-13 |

**Reported phenotype names (ClinVar):** not provided, none provided.

### 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 1096144). 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.*