Is COX6A2 p.Pro71His (c.212C>A) pathogenic?

COX6A2 p.Pro71His (c.212C>A) is classified Uncertain significance in COX6A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: ambiguous (0.3432); Absent from gnomAD v4.1.

How common is COX6A2 p.Pro71His (c.212C>A) in the general population?

COX6A2 p.Pro71His (c.212C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COX6A2 p.Pro71His (c.212C>A)?

AlphaMissense predicts ambiguous (score 0.3432) — an in-silico prediction, not a clinical call.

COX6A2 p.Pro71His

c.212C>A · VCV4233022

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3432 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,385,870)

Computational evidence

Protein change
AlphaMissense	0.3432	ambiguous
REVEL	0.429	indeterminate
SaProt	LLR -12.90	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP -0.35, phastCons 1
Regional constraint	o/e 1.26	unconstrained · MANE · 548 bp · p 0.002 · regional, not allelic
Overall
CADD	22.8	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

No allele count reported in gnomAD v4.1 (AN 1,385,870). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: COX6A2
Protein: p.Pro71His
Coding: c.212C>A
MANE Select: NM_005205
Type: single nucleotide variant
Location: chr16:31427856 (GRCh38)
Gene constraint: LOEUF 1.913 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.30

Full COX6A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COX6A2 p.Pro71Ser Uncertain significance ★ ⚠ same residue
COX6A2 p.Leu81Val Uncertain significance ★★ ⚠ same type
COX6A2 p.Ser39Arg Likely pathogenic ★ ⚠ same type
COX6A2 p.Ala2Thr Uncertain significance ★ ⚠ same type
COX6A2 p.Arg54Leu Uncertain significance ★ ⚠ same type
COX6A2 p.Arg60Cys Uncertain significance ★ ⚠ same type
COX6A2 p.Arg66Gly Uncertain significance ★ ⚠ same type
COX6A2 p.Arg68His 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/cox6a2-p-pro71his (accessed [today's date]).

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