Is COMMD6 p.Val30Met (c.88G>A) pathogenic?

COMMD6 p.Val30Met (c.88G>A) is classified Uncertain significance in COMMD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). AlphaMissense: likely benign (0.2368); Very rare (popmax 0.00401%, afr).

How common is COMMD6 p.Val30Met (c.88G>A) in the general population?

COMMD6 p.Val30Met (c.88G>A) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about COMMD6 p.Val30Met (c.88G>A)?

AlphaMissense predicts likely benign (score 0.2368) — an in-silico prediction, not a clinical call.

COMMD6 p.Val30Met

c.88G>A · VCV4232725

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2368 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2368	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -4.29	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 7.5	GERP 2.4, phastCons 1
Regional constraint	o/e 1.21	unconstrained · MANE · 11 kb · p 0.033 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,872 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000372% 6/1,612,322 alleles · very rare exomes 3/1,460,144 · genomes 3/152,178 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,957
Remaining individualsnot grpmax-eligible	0.0032%	31,210
East Asian	0.00223%	44,860

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: COMMD6
Protein: p.Val30Met
Coding: c.88G>A
MANE Select: NM_203495
Type: single nucleotide variant
Location: chr13:75530233 (GRCh38)
Gene constraint: LOEUF 1.538 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 85.37 · 3 PDB
Residue 30: the comm domain; a β-strand

Full COMMD6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COMMD6 p.Ala50Pro Uncertain significance ★ ⚠ same type
COMMD6 p.Asp33Asn Uncertain significance ★ ⚠ same type
COMMD6 p.Ile82Thr Uncertain significance ★ ⚠ same type
COMMD6 p.Lys57Asn Uncertain significance ★ ⚠ same type
COMMD6 p.Met28Val Uncertain significance ★ ⚠ same type
COMMD6 p.Met46Ile Uncertain significance ★ ⚠ same type
COMMD6 p.Phe61Ser 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/commd6-p-val30met (accessed [today's date]).

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