Is COX15 p.Ala286Val (c.857C>T) pathogenic?

COX15 p.Ala286Val (c.857C>T) is classified Uncertain significance in COX15 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-27). AlphaMissense: likely pathogenic (0.9853); Very rare (popmax 0.00333%, amr).

How common is COX15 p.Ala286Val (c.857C>T) in the general population?

COX15 p.Ala286Val (c.857C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about COX15 p.Ala286Val (c.857C>T)?

AlphaMissense predicts likely pathogenic (score 0.9853) — an in-silico prediction, not a clinical call.

COX15 p.Ala286Val

c.857C>T · rs1564646098 · VCV2062141

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9853 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9853	likely pathogenic · top 7% in COX15
REVEL	0.945	strongly pathogenic-leaning
SaProt	LLR -11.10	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	GERP 1.8, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 17 kb · p 0.00029 · regional, not allelic
Overall
CADD	32.0	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

Grpmax group 0.00333% Admixed American · 2/60,012 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000137% 2/1,461,890 alleles · very rare

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: COX15
Protein: p.Ala286Val
Coding: c.857C>T
MANE Select: NM_078470
dbSNP: rs1564646098
Type: single nucleotide variant
Location: chr10:99718476 (GRCh38)
Gene constraint: LOEUF 1.198 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.29

Full COX15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COX15 c.272+2T>G Pathogenic/Likely pathogenic ★★ same type
COX15 c.750+1G>A Likely pathogenic ★★ same type
COX15 c.750+1G>T Likely pathogenic ★★ same type
COX15 p.Arg153Ter Pathogenic/Likely pathogenic ★★ same type
COX15 p.Arg217Trp Pathogenic ★★ same type
COX15 p.Ser151Ter Pathogenic/Likely pathogenic ★★ same type
COX15 p.Ser229Ter Pathogenic/Likely pathogenic ★★ same type
COX15 p.Ser277Ter Pathogenic/Likely pathogenic ★★ 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/cox15-p-ala286val (accessed [today's date]).

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