Is COMMD4 p.Asp13Glu (c.39C>G) pathogenic?

COMMD4 p.Asp13Glu (c.39C>G) is classified Uncertain significance in COMMD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-06). AlphaMissense: likely pathogenic (0.9111); Very rare (popmax 0.00401%, afr).

How common is COMMD4 p.Asp13Glu (c.39C>G) in the general population?

COMMD4 p.Asp13Glu (c.39C>G) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about COMMD4 p.Asp13Glu (c.39C>G)?

AlphaMissense predicts likely pathogenic (score 0.9111) — an in-silico prediction, not a clinical call.

COMMD4 p.Asp13Glu

c.39C>G · VCV3835500

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9111 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9111	likely pathogenic
REVEL	0.433	indeterminate
SaProt	LLR -9.65	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 0.15, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 3,912 bp · p 0.66 · regional, not allelic
Overall
CADD	22.6	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 0.00401% African / African-American · 3/74,770 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000249% 4/1,608,764 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,923
East Asian	0.00224%	44,732

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.Asp13Glu
Coding: c.39C>G
MANE Select: NM_017828
Type: single nucleotide variant
Location: chr15:75338097 (GRCh38)
Gene constraint: LOEUF 0.982 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.85 · 4 PDB
Residue 13: 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.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

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-asp13glu (accessed [today's date]).

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