Is COMMD5 p.Val129Met (c.385G>A) pathogenic?

COMMD5 p.Val129Met (c.385G>A) is classified Uncertain significance in COMMD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-22). AlphaMissense: likely benign (0.1586); Very rare (popmax 0.00663%, sas).

How common is COMMD5 p.Val129Met (c.385G>A) in the general population?

COMMD5 p.Val129Met (c.385G>A) is very rare (popmax 0.00663%, sas) (gnomAD).

What do computational predictors say about COMMD5 p.Val129Met (c.385G>A)?

AlphaMissense predicts likely benign (score 0.1586) — an in-silico prediction, not a clinical call.

COMMD5 p.Val129Met

c.385G>A · VCV4832304

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1586 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00663%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1586	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -9.92	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	GERP 1.5, phastCons 0.99
Regional constraint	o/e 0.81	unconstrained · MANE · 671 bp · p 0.0015 · regional, not allelic
Overall
CADD	19.55	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 0.00663% South Asian · 6/90,546 alleles

Filtering AF 0.00288% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00196%

Overall 0.00267% 43/1,609,190 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00663%	15,091
Remaining individualsnot grpmax-eligible	0.00482%	20,736
African / African-American	0.00401%	24,950
European (non-Finnish)	0.00255%	39,281
Admixed American	0.00168%	59,382

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: COMMD5
Protein: p.Val129Met
Coding: c.385G>A
MANE Select: NM_014066
Type: single nucleotide variant
Location: chr8:144850954 (GRCh38)
Gene constraint: LOEUF 1.752 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.49 · 4 PDB
Residue 129: an α-helix

Full COMMD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ZNF7 p.Glu129Asp Uncertain significance ★ ⚠ same residue
COMMD5 p.Ala153Thr Uncertain significance ★ ⚠ same type
COMMD5 p.Arg135Gln Uncertain significance ★ ⚠ same type
COMMD5 p.Arg158Trp Uncertain significance ★ ⚠ same type
COMMD5 p.Arg201Gln Uncertain significance ★ ⚠ same type
COMMD5 p.Arg217Ser Uncertain significance ★ ⚠ same type
COMMD5 p.Arg220His Uncertain significance ★ ⚠ same type
COMMD5 p.Arg65Gln 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/commd5-p-val129met (accessed [today's date]).

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