Is COMMD4 p.Ala103Val (c.308C>T) pathogenic?

COMMD4 p.Ala103Val (c.308C>T) is classified Uncertain significance in COMMD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-10). AlphaMissense: likely benign (0.2822); Ultra-rare (popmax 0.0473%, eas).

How common is COMMD4 p.Ala103Val (c.308C>T) in the general population?

COMMD4 p.Ala103Val (c.308C>T) is ultra-rare (popmax 0.0473%, eas) (gnomAD).

What do computational predictors say about COMMD4 p.Ala103Val (c.308C>T)?

AlphaMissense predicts likely benign (score 0.2822) — an in-silico prediction, not a clinical call.

COMMD4 p.Ala103Val

c.308C>T · VCV3495899

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2822 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0473%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2822	likely benign
REVEL	0.158	moderately benign-leaning
SaProt	LLR -11.39	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.4, phastCons 0.99
Regional constraint	o/e 0.97	unconstrained · MANE · 3,912 bp · p 0.66 · regional, not allelic
Overall
CADD	23.7	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

Grpmax group 0.0473% East Asian · 21/44,438 alleles

Filtering AF 0.0316% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0266%

Overall 0.00378% 61/1,611,694 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0473%	2,116
South Asian	0.0132%	7,580
African / African-American	0.008%	12,495
European (non-Finnish)	0.00186%	53,637

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: COMMD4
Protein: p.Ala103Val
Coding: c.308C>T
MANE Select: NM_017828
Type: single nucleotide variant
Location: chr15:75339270 (GRCh38)
Gene constraint: LOEUF 0.982 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.85 · 4 PDB
Residue 103: 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 residue
COMMD4 p.Ala132Thr Uncertain significance ★ ⚠ same type
COMMD4 p.Ala163Thr Uncertain significance ★ ⚠ same type
COMMD4 p.Ala191Thr 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-ala103val (accessed [today's date]).

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