Is COX10 p.Ala438Thr (c.1312G>A) pathogenic?

COX10 p.Ala438Thr (c.1312G>A) is classified Uncertain significance in COX10 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-07). AlphaMissense: likely benign (0.0718); Very rare (popmax 0.00401%, afr).

How common is COX10 p.Ala438Thr (c.1312G>A) in the general population?

COX10 p.Ala438Thr (c.1312G>A) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about COX10 p.Ala438Thr (c.1312G>A)?

AlphaMissense predicts likely benign (score 0.0718) — an in-silico prediction, not a clinical call.

COX10 p.Ala438Thr

c.1312G>A · rs868542723 · VCV2191195

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0718 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0718	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -6.88	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 -2.2	GERP -2.4
Regional constraint	o/e 0.89	unconstrained · MANE · 372 bp · p 0.13 · regional, not allelic
Overall
CADD	0.559	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00401% African / African-American · 3/74,810 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000313% 5/1,598,414 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,937
East Asian	0.00223%	44,782
European (non-Finnish)	8.51e-05%	1,174,750

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: COX10
Protein: p.Ala438Thr
Coding: c.1312G>A
MANE Select: NM_001303
dbSNP: rs868542723
Type: single nucleotide variant
Location: chr17:14207193 (GRCh38)
Gene constraint: LOEUF 0.934 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.11

Full COX10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COX10 p.Asp336Val Pathogenic/Likely pathogenic ★★ same type
COX10 p.Gln230Ter Likely pathogenic ★★ same type
COX10 p.Pro225Leu Likely pathogenic ★★ same type
COX10 c.-89G>C Uncertain significance ★★ same type
COX10 c.-89G>T Uncertain significance ★★ same type
COX10 p.Ala174Thr Uncertain significance ★★ ⚠ same type
COX10 p.Ala175Ser Uncertain significance ★★ ⚠ same type
COX10 p.Ala175Val 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/cox10-p-ala438thr (accessed [today's date]).

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