Is COX15 p.Ser309Phe (c.926C>T) pathogenic?

COX15 p.Ser309Phe (c.926C>T) is classified Uncertain significance in COX15 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-30). AlphaMissense: likely benign (0.2098); Very rare (popmax 0.0022%, sas); Associated with Inborn genetic diseases.

What condition is associated with COX15 p.Ser309Phe (c.926C>T)?

COX15 p.Ser309Phe (c.926C>T) is associated with Inborn genetic diseases (ClinVar).

How common is COX15 p.Ser309Phe (c.926C>T) in the general population?

COX15 p.Ser309Phe (c.926C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about COX15 p.Ser309Phe (c.926C>T)?

AlphaMissense predicts likely benign (score 0.2098) — an in-silico prediction, not a clinical call.

COX15 p.Ser309Phe

c.926C>T · rs1278838654 · VCV2143991

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2098 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2098	likely benign
REVEL	0.79	moderately pathogenic-leaning
SaProt	LLR -10.21	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.20	gain · loss 0.00 · not in the SpliceAI release · independent
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	31.0	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 0.0022% South Asian · 2/91,082 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00186% 30/1,613,972 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0064%	15,621
South Asiangrpmax	0.0022%	45,541
European (non-Finnish)	0.00186%	53,636
Finnishnot grpmax-eligible	0.00156%	64,022
African / African-American	0.00134%	74,906

Remaining individuals shows a higher raw frequency than the grpmax group above it. 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.

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.Ser309Phe
Coding: c.926C>T
MANE Select: NM_078470
dbSNP: rs1278838654
Type: single nucleotide variant
Location: chr10:99718407 (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-ser309phe (accessed [today's date]).

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