Is COX7B p.Ala57Ser (c.169G>T) pathogenic?

COX7B p.Ala57Ser (c.169G>T) is classified Uncertain significance in COX7B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-07). AlphaMissense: likely benign (0.1123); Very rare (popmax 0.00296%, eas).

How common is COX7B p.Ala57Ser (c.169G>T) in the general population?

COX7B p.Ala57Ser (c.169G>T) is very rare (popmax 0.00296%, eas) (gnomAD).

What do computational predictors say about COX7B p.Ala57Ser (c.169G>T)?

AlphaMissense predicts likely benign (score 0.1123) — an in-silico prediction, not a clinical call.

COX7B p.Ala57Ser

c.169G>T · rs782772132 · VCV1971573

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1123 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00296%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1123	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -9.07	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 3.8	GERP -0.47, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 5,704 bp · p 0.27 · regional, not allelic
Overall
CADD	15.53	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 0.00296% East Asian · 1/33,767 alleles

Filtering AF 0.00151% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00129%

Overall 0.00191% 23/1,204,840 alleles · very rare exomes 21/1,092,837 · genomes 2/112,003 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00296%	33,767
European (non-Finnish)	0.00236%	42,422
Finnishnot grpmax-eligible	0.00215%	46,592

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: COX7B
Protein: p.Ala57Ser
Coding: c.169G>T
MANE Select: NM_001866
dbSNP: rs782772132
Type: single nucleotide variant
Location: chrX:77905187 (GRCh38)
Structure: AlphaFold pLDDT 90.15 · 3 PDB

Full COX7B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COX7B p.Arg29His Uncertain significance ★★ ⚠ same type
COX7B c.165+10A>G Benign ★★ same type
COX7B c.*82G>T Likely benign ★★ same type
COX7B p.Ser16Arg Benign ★★ same type
COX7B c.40+5G>C Likely pathogenic ★ same type
COX7B p.Asn79Asp Uncertain significance ★ ⚠ same type
COX7B p.Leu66Val Uncertain significance ★ ⚠ same type
COX7B p.Lys36Arg Conflicting classifications of pathogenicity ★ ⚠ 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/cox7b-p-ala57ser (accessed [today's date]).

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