Is COA7 p.Ala92Val (c.275C>T) pathogenic?

COA7 p.Ala92Val (c.275C>T) is classified Uncertain significance in COA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-01). AlphaMissense: likely pathogenic (0.8638); No allele count reported in gnomAD v4.1 (AN 1,612,154).

How common is COA7 p.Ala92Val (c.275C>T) in the general population?

COA7 p.Ala92Val (c.275C>T) is no allele count reported in gnomAD v4.1 (AN 1,612,154) (gnomAD).

What do computational predictors say about COA7 p.Ala92Val (c.275C>T)?

AlphaMissense predicts likely pathogenic (score 0.8638) — an in-silico prediction, not a clinical call.

COA7 p.Ala92Val

c.275C>T · rs2149903533 · VCV1334978

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8638 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,154)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8638	likely pathogenic
REVEL	0.678	pathogenic-leaning
SaProt	LLR -14.45	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 5,078 bp · p 0.00048 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,612,154). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: COA7
Protein: p.Ala92Val
Coding: c.275C>T
MANE Select: NM_023077
dbSNP: rs2149903533
Type: single nucleotide variant
Location: chr1:52688141 (GRCh38)
Gene constraint: LOEUF 0.867 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 95.47 · 1 PDB
Residue 92: an α-helix

Full COA7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COA7 p.Glu220Gln Uncertain significance ★★ ⚠ same type
COA7 p.Glu31Lys Uncertain significance ★★ ⚠ same type
COA7 p.Gly84Asp Uncertain significance ★★ ⚠ same type
COA7 p.Tyr38Cys Uncertain significance ★★ ⚠ same type
COA7 c.107-20C>G Benign/Likely benign ★★ same type
COA7 c.107-5C>T Likely benign ★★ same type
COA7 c.248-145C>T Benign ★★ same type
COA7 c.248-36C>G Benign ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/coa7-p-ala92val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown