Is COMMD10 p.Val19Ala (c.56T>C) pathogenic?

COMMD10 p.Val19Ala (c.56T>C) is classified Uncertain significance in COMMD10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-03). AlphaMissense: likely benign (0.2909); Very rare (popmax 0.00223%, eas).

How common is COMMD10 p.Val19Ala (c.56T>C) in the general population?

COMMD10 p.Val19Ala (c.56T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about COMMD10 p.Val19Ala (c.56T>C)?

AlphaMissense predicts likely benign (score 0.2909) — an in-silico prediction, not a clinical call.

COMMD10 p.Val19Ala

c.56T>C · VCV4005680

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2909 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2909	likely benign
REVEL	0.436	indeterminate
SaProt	LLR -10.77	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.8, phastCons 1
Regional constraint	o/e 1.33	unconstrained · MANE · 207 kb · p 5.3e-07 · regional, not allelic
Overall
CADD	26.4	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 0.00223% East Asian · 1/44,852 alleles

Overall 6.87e-05% 1/1,456,158 alleles · very rare

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: COMMD10
Protein: p.Val19Ala
Coding: c.56T>C
MANE Select: NM_016144
Type: single nucleotide variant
Location: chr5:116087511 (GRCh38)
Gene constraint: LOEUF 1.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.19 · 6 PDB
Residue 19: an α-helix

Full COMMD10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COMMD10 p.Ala196Thr Uncertain significance ★ ⚠ same type
COMMD10 p.Ala2Pro Uncertain significance ★ ⚠ same type
COMMD10 p.Ala5Thr Uncertain significance ★ ⚠ same type
COMMD10 p.Ala90Val Uncertain significance ★ ⚠ same type
COMMD10 p.Arg125Gln Uncertain significance ★ ⚠ same type
COMMD10 p.Arg125Trp Uncertain significance ★ ⚠ same type
COMMD10 p.Arg36Trp Uncertain significance ★ ⚠ same type
COMMD10 p.Asn166Lys 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/commd10-p-val19ala (accessed [today's date]).

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