Is COMMD5 p.Gln143Arg (c.428A>G) pathogenic?

COMMD5 p.Gln143Arg (c.428A>G) is classified Likely benign in COMMD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-06). AlphaMissense: likely benign (0.0566); Absent from gnomAD v4.1.

How common is COMMD5 p.Gln143Arg (c.428A>G) in the general population?

COMMD5 p.Gln143Arg (c.428A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COMMD5 p.Gln143Arg (c.428A>G)?

AlphaMissense predicts likely benign (score 0.0566) — an in-silico prediction, not a clinical call.

COMMD5 p.Gln143Arg

c.428A>G · VCV4005694

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0566 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0566	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -6.31	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 -0.38	GERP -3.1, phastCons 0.001
Regional constraint	o/e 0.81	unconstrained · MANE · 671 bp · p 0.0015 · regional, not allelic
Overall
CADD	5.304	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COMMD5
Protein: p.Gln143Arg
Coding: c.428A>G
MANE Select: NM_014066
Type: single nucleotide variant
Location: chr8:144850911 (GRCh38)
Gene constraint: LOEUF 1.752 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.49 · 4 PDB
Residue 143: an α-helix

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

Similar variants

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
COMMD5 p.Arg70His 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-gln143arg (accessed [today's date]).

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