Is COX6A1 p.Ala28Pro (c.82G>C) pathogenic?

COX6A1 p.Ala28Pro (c.82G>C) is classified Uncertain significance in COX6A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-24). AlphaMissense: likely benign (0.1608); Absent from gnomAD v4.1.

How common is COX6A1 p.Ala28Pro (c.82G>C) in the general population?

COX6A1 p.Ala28Pro (c.82G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COX6A1 p.Ala28Pro (c.82G>C)?

AlphaMissense predicts likely benign (score 0.1608) — an in-silico prediction, not a clinical call.

COX6A1 p.Ala28Pro

c.82G>C · rs1592976675 · VCV2102840

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1608 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1608	likely benign
REVEL	0.271	benign-leaning
SaProt	LLR -11.17	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.8, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 2,407 bp · p 0.91 · regional, not allelic
Overall
CADD	21.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COX6A1
Protein: p.Ala28Pro
Coding: c.82G>C
MANE Select: NM_004373
dbSNP: rs1592976675
Type: single nucleotide variant
Location: chr12:120438208 (GRCh38)
Gene constraint: LOEUF 1.355 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 84.06 · 3 PDB

Full COX6A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COX6A1 p.Ala28Val Uncertain significance ★ ⚠ same residue
COX6A1 p.Ala28= Likely benign ★ same residue
COX6A1 c.103+1G>C Uncertain significance ★★ same type
COX6A1 p.Ala2Ser Uncertain significance ★★ ⚠ same type
COX6A1 p.Arg11Pro Uncertain significance ★★ ⚠ same type
COX6A1 p.Arg17His Uncertain significance ★★ ⚠ same type
COX6A1 p.Arg36Cys Uncertain significance ★★ ⚠ same type
COX6A1 p.Glu107Lys 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/cox6a1-p-ala28pro (accessed [today's date]).

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