Is COX6C p.Ala24Val (c.71C>T) pathogenic?

COX6C p.Ala24Val (c.71C>T) is classified Likely benign in COX6C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: likely benign (0.0684); Very rare (popmax 0.00169%, nfe).

How common is COX6C p.Ala24Val (c.71C>T) in the general population?

COX6C p.Ala24Val (c.71C>T) is very rare (popmax 0.00169%, nfe) (gnomAD).

What do computational predictors say about COX6C p.Ala24Val (c.71C>T)?

AlphaMissense predicts likely benign (score 0.0684) — an in-silico prediction, not a clinical call.

COX6C p.Ala24Val

c.71C>T · VCV4233029

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0684 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00169%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0684	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -6.69	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP -0.24, phastCons 0.088
Regional constraint	o/e 1.04	unconstrained · MANE · 4,513 bp · p 0.71 · regional, not allelic
Overall
CADD	0.908	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

Grpmax group 0.00169% European (non-Finnish) · 20/1,180,024 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00136% 22/1,613,970 alleles · very rare exomes 20/1,461,746 · genomes 2/152,224 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,244
European (non-Finnish)grpmax	0.00169%	59,001

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: COX6C
Protein: p.Ala24Val
Coding: c.71C>T
MANE Select: NM_004374
Type: single nucleotide variant
Location: chr8:99891951 (GRCh38)
Gene constraint: LOEUF 1.231 · pLI 0.33 (gnomAD)
Structure: AlphaFold pLDDT 94.94 · 3 PDB

Full COX6C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COX6C p.Ala16Ser Uncertain significance ★ ⚠ same type
COX6C p.Arg18His Uncertain significance ★ ⚠ same type
COX6C p.Arg40His Uncertain significance ★ ⚠ same type
COX6C p.Arg66Lys Uncertain significance ★ ⚠ same type
COX6C p.Asn21Ser Uncertain significance ★ ⚠ same type
COX6C p.Glu4Gln Uncertain significance ★ ⚠ same type
COX6C p.Glu64Asp Uncertain significance ★ ⚠ same type
COX6C p.Lys8Glu 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/cox6c-p-ala24val (accessed [today's date]).

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