Is COX6A1 p.Phe43= (c.129C>T) pathogenic?

COX6A1 p.Phe43= (c.129C>T) is classified Likely benign in COX6A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-19). Very rare (popmax 0.000558%).

How common is COX6A1 p.Phe43= (c.129C>T) in the general population?

COX6A1 p.Phe43= (c.129C>T) is very rare (popmax 0.000558%) (gnomAD).

COX6A1 p.Phe43=

c.129C>T · VCV3691493

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000558%)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.028	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.32	GERP -2.7, phastCons 0.019
Overall
CADD	10.47	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000558%

Overall 0.000558% 9/1,614,124 alleles · very rare

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.Phe43=
Coding: c.129C>T
MANE Select: NM_004373
Type: single nucleotide variant
Location: chr12:120438404 (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 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
COX6A1 p.His62Tyr Uncertain significance ★★ ⚠ same type
COX6A1 p.His98Tyr 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-phe43 (accessed [today's date]).

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