Is COMMD2 p.Val62Met (c.184G>A) pathogenic?

COMMD2 p.Val62Met (c.184G>A) is classified Uncertain significance in COMMD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-30). AlphaMissense: likely pathogenic (0.6239); Rare (popmax 0.127%, eas).

How common is COMMD2 p.Val62Met (c.184G>A) in the general population?

COMMD2 p.Val62Met (c.184G>A) is rare (popmax 0.127%, eas) (gnomAD).

What do computational predictors say about COMMD2 p.Val62Met (c.184G>A)?

AlphaMissense predicts likely pathogenic (score 0.6239) — an in-silico prediction, not a clinical call.

COMMD2 p.Val62Met

c.184G>A · rs534739227 · VCV3147909

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6239 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.127%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6239	likely pathogenic
REVEL	0.302	indeterminate
SaProt	LLR -10.60	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 11 kb · p 0.52 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.127% East Asian · 57/44,870 alleles

Filtering AF 0.101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0912%

Overall 0.00409% 66/1,613,926 alleles · rare exomes 60/1,461,574 · genomes 6/152,352 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.127%	787
Remaining individualsnot grpmax-eligible	0.008%	12,498
Admixed American	0.00334%	29,982
European (non-Finnish)	0.00017%	589,967

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: COMMD2
Protein: p.Val62Met
Coding: c.184G>A
MANE Select: NM_016094
dbSNP: rs534739227
Type: single nucleotide variant
Location: chr3:149751447 (GRCh38)
Gene constraint: LOEUF 1.611 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.00 · 3 PDB
Residue 62: an α-helix

Full COMMD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COMMD2 p.Ala118Val Uncertain significance ★ ⚠ same type
COMMD2 p.Ala136Thr Uncertain significance ★ ⚠ same type
COMMD2 p.Ala170Thr Uncertain significance ★ ⚠ same type
COMMD2 p.Arg130Gln Uncertain significance ★ ⚠ same type
COMMD2 p.Arg196His Uncertain significance ★ same type
COMMD2 p.Arg196Leu Uncertain significance ★ ⚠ same type
COMMD2 p.Arg29Leu Uncertain significance ★ ⚠ same type
COMMD2 p.Arg29Trp 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/commd2-p-val62met (accessed [today's date]).

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