Is COMMD4 p.Ala191Thr (c.571G>A) pathogenic?

COMMD4 p.Ala191Thr (c.571G>A) is classified Uncertain significance in COMMD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-19). AlphaMissense: ambiguous (0.3455); Absent from gnomAD v4.1.

How common is COMMD4 p.Ala191Thr (c.571G>A) in the general population?

COMMD4 p.Ala191Thr (c.571G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COMMD4 p.Ala191Thr (c.571G>A)?

AlphaMissense predicts ambiguous (score 0.3455) — an in-silico prediction, not a clinical call.

COMMD4 p.Ala191Thr

c.571G>A · VCV3835503

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3455 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3455	ambiguous
REVEL	0.236	benign-leaning
SaProt	LLR -10.58	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 3,912 bp · p 0.66 · regional, not allelic
Overall
CADD	27.5	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: COMMD4
Protein: p.Ala191Thr
Coding: c.571G>A
MANE Select: NM_017828
Type: single nucleotide variant
Location: chr15:75339976 (GRCh38)
Gene constraint: LOEUF 0.982 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.85 · 4 PDB
Residue 191: the comm domain; an α-helix

Full COMMD4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COMMD4 p.Ala103Thr Uncertain significance ★ ⚠ same type
COMMD4 p.Ala103Val Uncertain significance ★ ⚠ same type
COMMD4 p.Ala132Thr Uncertain significance ★ ⚠ same type
COMMD4 p.Ala163Thr Uncertain significance ★ ⚠ same type
COMMD4 p.Arg108His Uncertain significance ★ ⚠ same type
COMMD4 p.Arg122Trp Uncertain significance ★ ⚠ same type
COMMD4 p.Arg127Gly Uncertain significance ★ ⚠ same type
COMMD4 p.Arg137Gln 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/commd4-p-ala191thr (accessed [today's date]).

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