Is COX7B p.Asn79Asp (c.235A>G) pathogenic?

COX7B p.Asn79Asp (c.235A>G) is classified Uncertain significance in COX7B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-15). AlphaMissense: likely benign (0.0494); Ultra-rare (popmax 0.0608%, mid).

How common is COX7B p.Asn79Asp (c.235A>G) in the general population?

COX7B p.Asn79Asp (c.235A>G) is ultra-rare (popmax 0.0608%, mid) (gnomAD).

What do computational predictors say about COX7B p.Asn79Asp (c.235A>G)?

AlphaMissense predicts likely benign (score 0.0494) — an in-silico prediction, not a clinical call.

COX7B p.Asn79Asp

c.235A>G · rs781812051 · VCV2762405

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0494 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0608%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0494	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -1.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.7	GERP 0.45, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 5,704 bp · p 0.27 · regional, not allelic
Overall
CADD	5.023	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 0.0608% Middle Eastern · 2/3,292 alleles

Filtering AF 0.0107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00449%

Overall 0.00167% 20/1,196,547 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0608%	1,646
African / African-American	0.00527%	18,960
European (non-Finnish)	0.0017%	58,960

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.Asn79Asp
Coding: c.235A>G
MANE Select: NM_001866
dbSNP: rs781812051
Type: single nucleotide variant
Location: chrX:77905253 (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.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-asn79asp (accessed [today's date]).

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