Is COX15 p.Val334Phe (c.1000G>T) pathogenic?

COX15 p.Val334Phe (c.1000G>T) is classified Conflicting classifications of pathogenicity in COX15 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2024-11-20). AlphaMissense: likely benign (0.1895); Very rare (popmax 0.00569%, nfe); Associated with Inborn genetic diseases.

What condition is associated with COX15 p.Val334Phe (c.1000G>T)?

COX15 p.Val334Phe (c.1000G>T) is associated with Inborn genetic diseases (ClinVar).

How common is COX15 p.Val334Phe (c.1000G>T) in the general population?

COX15 p.Val334Phe (c.1000G>T) is very rare (popmax 0.00569%, nfe) (gnomAD).

What do computational predictors say about COX15 p.Val334Phe (c.1000G>T)?

AlphaMissense predicts likely benign (score 0.1895) — an in-silico prediction, not a clinical call.

COX15 p.Val334Phe

c.1000G>T · rs771639452 · VCV214251

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1895 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00569%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1895	likely benign
REVEL	0.378	indeterminate
SaProt	LLR -9.28	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 2, phastCons 0.99
Regional constraint	o/e 0.84	unconstrained · MANE · 17 kb · p 0.00029 · regional, not allelic
Overall
CADD	20.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00569% European (non-Finnish) · 67/1,177,084 alleles

Filtering AF 0.00455% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00418%

Overall 0.00422% 68/1,610,556 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00569%	17,568
Remaining individualsnot grpmax-eligible	0.0016%	62,370

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.Val334Phe
Coding: c.1000G>T
MANE Select: NM_078470
dbSNP: rs771639452
Type: single nucleotide variant
Location: chr10:99716449 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COX15 p.Arg153Gln Uncertain significance ★★ ⚠ same condition
COX15 p.Arg183Cys Uncertain significance ★★ ⚠ same condition
COX15 p.Arg67Gln Uncertain significance ★★ ⚠ same condition
COX15 p.Arg67Trp Uncertain significance ★★ ⚠ same condition
COX15 p.Gln2Arg Uncertain significance ★★ ⚠ same condition
COX15 p.Gly179Ser Uncertain significance ★★ ⚠ same condition
COX15 p.Gly182Arg Uncertain significance ★★ ⚠ same condition
COX15 p.Gly41Glu Uncertain significance ★★ ⚠ same condition

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-val334phe (accessed [today's date]).

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