Is COX15 p.Phe121Ser (c.362T>C) pathogenic?

COX15 p.Phe121Ser (c.362T>C) is classified Uncertain significance in COX15 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-01). AlphaMissense: likely pathogenic (0.9886); Absent from gnomAD v4.1.

How common is COX15 p.Phe121Ser (c.362T>C) in the general population?

COX15 p.Phe121Ser (c.362T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COX15 p.Phe121Ser (c.362T>C)?

AlphaMissense predicts likely pathogenic (score 0.9886) — an in-silico prediction, not a clinical call.

COX15 p.Phe121Ser

c.362T>C · rs2036997384 · VCV916222

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9886 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9886	likely pathogenic · top 5% in COX15
REVEL	0.952	strongly pathogenic-leaning
SaProt	LLR -15.80	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 11	GERP 1.7, 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COX15
Protein: p.Phe121Ser
Coding: c.362T>C
MANE Select: NM_078470
dbSNP: rs2036997384
Type: single nucleotide variant
Location: chr10:99727474 (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-phe121ser (accessed [today's date]).

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