Is COMMD10 p.Leu134Val (c.400C>G) pathogenic?

COMMD10 p.Leu134Val (c.400C>G) is classified Uncertain significance in COMMD10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-17). AlphaMissense: likely benign (0.1808); Absent from gnomAD v4.1.

How common is COMMD10 p.Leu134Val (c.400C>G) in the general population?

COMMD10 p.Leu134Val (c.400C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COMMD10 p.Leu134Val (c.400C>G)?

AlphaMissense predicts likely benign (score 0.1808) — an in-silico prediction, not a clinical call.

COMMD10 p.Leu134Val

c.400C>G · VCV4655787

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1808 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1808	likely benign
REVEL	0.263	benign-leaning
SaProt	LLR -10.28	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 4.7	GERP 2, phastCons 1
Regional constraint	o/e 1.33	unconstrained · MANE · 207 kb · p 5.3e-07 · regional, not allelic
Overall
CADD	26.1	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: COMMD10
Protein: p.Leu134Val
Coding: c.400C>G
MANE Select: NM_016144
Type: single nucleotide variant
Location: chr5:116134068 (GRCh38)
Gene constraint: LOEUF 1.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.19 · 6 PDB
Residue 134: a β-strand; the comm domain

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-leu134val (accessed [today's date]).

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