Is COX7B p.Pro3Ala (c.7C>G) pathogenic?

COX7B p.Pro3Ala (c.7C>G) is classified Uncertain significance in COX7B (ClinVar, Single submitter, 1 submitter; last evaluated 2017-03-03). AlphaMissense: likely benign (0.1101); Ultra-rare (popmax 0.0421%, afr).

How common is COX7B p.Pro3Ala (c.7C>G) in the general population?

COX7B p.Pro3Ala (c.7C>G) is ultra-rare (popmax 0.0421%, afr) (gnomAD).

What do computational predictors say about COX7B p.Pro3Ala (c.7C>G)?

AlphaMissense predicts likely benign (score 0.1101) — an in-silico prediction, not a clinical call.

COX7B p.Pro3Ala

c.7C>G · rs370681452 · VCV423717

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1101 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0421%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1101	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -5.84	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 0.71	GERP 0.64, phastCons 0.87
Regional constraint	o/e 0.86	unconstrained · MANE · 5,704 bp · p 0.27 · regional, not allelic
Overall
CADD	14.85	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 0.0421% African / African-American · 24/57,011 alleles

Filtering AF 0.029% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0247%

Overall 0.00215% 26/1,209,216 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0421%	2,375
Middle Eastern	0.0229%	4,374
Remaining individualsnot grpmax-eligible	0.0021%	47,572

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.Pro3Ala
Coding: c.7C>G
MANE Select: NM_001866
dbSNP: rs370681452
Type: single nucleotide variant
Location: chrX:77899560 (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.Ala57Ser Uncertain significance ★ ⚠ same type
COX7B p.Asn79Asp Uncertain significance ★ ⚠ same type
COX7B p.Leu66Val 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/cox7b-p-pro3ala (accessed [today's date]).

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