Is COX10 p.Asn204Ser (c.611A>G) pathogenic?

COX10 p.Asn204Ser (c.611A>G) is classified Uncertain significance in COX10 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-08). AlphaMissense: likely benign (0.2461); Very rare (popmax 0.00017%, nfe).

How common is COX10 p.Asn204Ser (c.611A>G) in the general population?

COX10 p.Asn204Ser (c.611A>G) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about COX10 p.Asn204Ser (c.611A>G)?

AlphaMissense predicts likely benign (score 0.2461) — an in-silico prediction, not a clinical call.

COX10 p.Asn204Ser

c.611A>G · rs1597501439 · VCV1915327

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2461 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2461	likely benign
REVEL	0.905	moderately pathogenic-leaning
SaProt	LLR -13.20	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 1.6, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 90 kb · p 0.97 · regional, not allelic
Overall
CADD	26.7	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 0.00017% European (non-Finnish) · 2/1,179,704 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,432 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: COX10
Protein: p.Asn204Ser
Coding: c.611A>G
MANE Select: NM_001303
dbSNP: rs1597501439
Type: single nucleotide variant
Location: chr17:14102229 (GRCh38)
Gene constraint: LOEUF 0.934 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.11
Residue 204: a UniProt-annotated variant site (in mc4dn3)

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

Similar variants

COX10 p.Asn204Lys Pathogenic same residue
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

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-asn204ser (accessed [today's date]).

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