Is COX6A1 p.Ala28= (c.84C>T) pathogenic?

COX6A1 p.Ala28= (c.84C>T) is classified Likely benign in COX6A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-11). Very rare (popmax 0.000339%, nfe).

How common is COX6A1 p.Ala28= (c.84C>T) in the general population?

COX6A1 p.Ala28= (c.84C>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

COX6A1 p.Ala28=

c.84C>T · rs905599042 · VCV1646679

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.025	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.82	GERP -2.4, phastCons 1
Overall
CADD	9.186	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,944 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,613,748 alleles · very rare exomes 1/1,461,566 · genomes 3/152,182 · joint denominator

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: COX6A1
Protein: p.Ala28=
Coding: c.84C>T
MANE Select: NM_004373
dbSNP: rs905599042
Type: single nucleotide variant
Location: chr12:120438210 (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.Ala28Pro Uncertain significance ★ ⚠ same residue
COX6A1 p.Ala28Val Uncertain significance ★ ⚠ 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-ala28 (accessed [today's date]).

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