Is COA8 p.Val3Ala (c.8T>C) pathogenic?

COA8 p.Val3Ala (c.8T>C) is classified Benign in COA8 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.0414); Common (popmax 9.05%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about COA8 p.Val3Ala (c.8T>C)?

AlphaMissense predicts likely benign (score 0.0414) — an in-silico prediction, not a clinical call.

COA8 p.Val3Ala

Q: How common is COA8 p.Val3Ala (c.8T>C) in the general population?

COA8 p.Val3Ala (c.8T>C) is common (popmax 9.05%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.8T>C · rs61733762 · VCV381843

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0414 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 9.05%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0414	likely benign
REVEL	0.094	moderately benign-leaning
SaProt	LLR -4.01	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.2	GERP -0.11
Regional constraint	o/e 1.16	unconstrained · MANE · 27 kb · p 0.018 · regional, not allelic
Overall
CADD	3.067	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V16A vs ClinVar V3A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.05% African / African-American · 6,704/74,056 alleles

Filtering AF 8.87% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.8%

Overall 0.494% 7,699/1,558,348 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.05%	11
Admixed American	0.694%	144
Remaining individualsnot grpmax-eligible	0.652%	153
Middle Eastern	0.619%	161
South Asian	0.0254%	3,929
European (non-Finnish)	0.0141%	7,105

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: COA8
Protein: p.Val3Ala
Coding: c.8T>C
MANE Select: NM_001370595
dbSNP: rs61733762
Type: single nucleotide variant
Location: chr14:103563009 (GRCh38)
Gene constraint: LOEUF 1.305 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.19

Full COA8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COA8 p.Val3= Likely benign ★ same residue
COA8 p.Arg66Ter Pathogenic ★★ same type
COA8 c.-32C>G Uncertain significance ★★ ⚠ same type
COA8 p.Ala140Val Uncertain significance ★★ ⚠ same type
COA8 p.Ala176Gly Uncertain significance ★★ ⚠ same type
COA8 p.Ala27Val Uncertain significance ★★ ⚠ same type
COA8 p.Arg164Cys Uncertain significance ★★ ⚠ same type
COA8 p.Arg17Leu Uncertain significance ★★ ⚠ 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/coa8-p-val3ala (accessed [today's date]).

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