Is COMMD9 p.Val124Ile (c.370G>A) pathogenic?

COMMD9 p.Val124Ile (c.370G>A) is classified Uncertain significance in COMMD9 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely benign (0.08); Absent from gnomAD v4.1.

How common is COMMD9 p.Val124Ile (c.370G>A) in the general population?

COMMD9 p.Val124Ile (c.370G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COMMD9 p.Val124Ile (c.370G>A)?

AlphaMissense predicts likely benign (score 0.08) — an in-silico prediction, not a clinical call.

COMMD9 p.Val124Ile

c.370G>A · rs1279553139 · VCV2241139

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.08 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.08	likely benign
REVEL	0.145	moderately benign-leaning
SaProt	LLR -8.48	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 1.3, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 15 kb · p 0.55 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: COMMD9
Protein: p.Val124Ile
Coding: c.370G>A
MANE Select: NM_014186
dbSNP: rs1279553139
Type: single nucleotide variant
Location: chr11:36276223 (GRCh38)
Gene constraint: LOEUF 1.513 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.27 · 7 PDB
Residue 124: a β-strand; the comm domain

Full COMMD9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COMMD9 p.Ala79= Benign ★★ same type
COMMD9 p.Ala57Ser Uncertain significance ★ ⚠ same type
COMMD9 p.Arg110Lys Uncertain significance ★ ⚠ same type
COMMD9 p.Arg122Cys Uncertain significance ★ ⚠ same type
COMMD9 p.Arg141His Uncertain significance ★ ⚠ same type
COMMD9 p.Arg187Cys Uncertain significance ★ ⚠ same type
COMMD9 p.Arg66Cys Uncertain significance ★ ⚠ same type
COMMD9 p.Arg74Cys 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/commd9-p-val124ile (accessed [today's date]).

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