# NM_001866.3(COX7B):c.180C>T (p.Val60=)

https://sugi.bio/variant/cox7b-p-val60

## Summary

**COX7B p.Val60= (c.180C>T)** is classified **Likely benign** in COX7B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-06). Very rare (popmax 0.00296%, eas).

**At a glance:** Likely benign · review: Single submitter · rsID rs782173769 · 1 submitter · very rare (popmax 0.00296%, eas)

## For patients & families {#patients}

This is a change in the COX7B 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 | [COX7B](https://sugi.bio/atlas/gene/COX7B/) |
| Protein change (HGVS p.) | p.Val60= |
| Coding change (HGVS c.) | c.180C>T |
| MANE Select transcript | [NM_001866](https://www.ncbi.nlm.nih.gov/nuccore/NM_001866) |
| dbSNP | [rs782173769](https://www.ncbi.nlm.nih.gov/snp/rs782173769/) |
| Variant type | single nucleotide variant |
| Location | chrX:77905198-77905198 (GRCh38) |
| ClinVar | [VCV2880995](https://www.ncbi.nlm.nih.gov/clinvar/variation/2880995/) |

**All HGVS expressions:** `LRG_1250:g.10735C>T`, `LRG_1250t1:c.180C>T`, `NC_000023.10:g.77160695C>T`, `NC_000023.11:g.77905198C>T`, `NG_033027.2:g.10735C>T`, `NM_001866.3:c.180C>T`

## 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 0.813, GERP -0.188, phastCons 1 — weakly conserved position
- CADD: **PHRED 1.078**. 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: **below the reporting threshold**. This position is scored for a different substitution (C>A, Δ0.27 acceptor loss), so this allele was evaluated and its deltas all fell under Δ0.2 — a prediction of no splicing effect for this allele, not a gap in our data. *No ACMG code assigned.*
- Population frequency (gnomAD v4.1): grpmax **0.00296%** (eas) · FAF95 0.000566% · FAF99 0.000413% · 1/33,736 in the highest group · 14/1,206,760 alleles overall — very rare (popmax 0.00296%, eas).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| Remaining individuals (not grpmax-eligible) | 0.00421% | 23,738 |
| East Asian (grpmax) | 0.00296% | 33,736 |
| Finnish (not grpmax-eligible) | 0.00215% | 46,515 |
| European (non-Finnish) | 0.00112% | 89,288 |

Remaining individuals shows a higher raw frequency than the grpmax group. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and "Remaining individuals" — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

*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** — Limited (XL)

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 90.15, 56% of residues very-high.

**3 experimental structure(s)** (PDB): [5Z62](https://www.rcsb.org/structure/5Z62), [9I6F](https://www.rcsb.org/structure/9I6F), [9I7U](https://www.rcsb.org/structure/9I7U).

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

*Describes the biological roles of COX7B (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.*


### Pathways affected {#pathways}

COX7B participates in **4 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [Complex IV assembly](https://reactome.org/content/detail/R-HSA-9864848) | curated |
| [Cytoprotection by HMOX1](https://reactome.org/content/detail/R-HSA-9707564) | curated |
| [Respiratory electron transport](https://reactome.org/content/detail/R-HSA-611105) | curated |
| [TP53 Regulates Metabolic Genes](https://reactome.org/content/detail/R-HSA-5628897) | curated |

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

**Biological process:** central nervous system development.

## Clinical significance {#significance}

**Likely benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2023-04-06.

**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 | 2023-04-06 |

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

## Similar variants {#similar}

Related COX7B variant pages (same residue, condition, or type): [COX7B p.Arg29His](/variant/cox7b-p-arg29his), [COX7B c.165+10A>G](/variant/cox7b-c-165-plus-10a-g), [COX7B c.*82G>T](/variant/cox7b-c-star-82g-t), [COX7B p.Ser16Arg](/variant/cox7b-p-ser16arg), [COX7B c.40+5G>C](/variant/cox7b-c-40-plus-5g-c), [COX7B p.Ala57Ser](/variant/cox7b-p-ala57ser), [COX7B p.Asn79Asp](/variant/cox7b-p-asn79asp), [COX7B p.Leu66Val](/variant/cox7b-p-leu66val).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); 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 2880995). 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.*