Is COMMD9 p.Val24Leu (c.70G>C) pathogenic?

COMMD9 p.Val24Leu (c.70G>C) is classified Uncertain significance in COMMD9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-03). AlphaMissense: ambiguous (0.46); Ultra-rare (popmax 0.0171%, nfe).

How common is COMMD9 p.Val24Leu (c.70G>C) in the general population?

COMMD9 p.Val24Leu (c.70G>C) is ultra-rare (popmax 0.0171%, nfe) (gnomAD).

What do computational predictors say about COMMD9 p.Val24Leu (c.70G>C)?

AlphaMissense predicts ambiguous (score 0.46) — an in-silico prediction, not a clinical call.

COMMD9 p.Val24Leu

c.70G>C · VCV3495917

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.46 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0171%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.46	ambiguous
REVEL	0.087	moderately benign-leaning
SaProt	LLR -7.68	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.1, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 15 kb · p 0.55 · regional, not allelic
Overall
CADD	23.2	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 0.0171% European (non-Finnish) · 199/1,166,254 alleles

Filtering AF 0.0151% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0144%

Overall 0.0134% 212/1,587,404 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0171%	5,861
Remaining individualsnot grpmax-eligible	0.0164%	6,116
African / African-American	0.00272%	36,774
Finnishnot grpmax-eligible	0.00158%	63,246

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: COMMD9
Protein: p.Val24Leu
Coding: c.70G>C
MANE Select: NM_014186
Type: single nucleotide variant
Location: chr11:36280819 (GRCh38)
Gene constraint: LOEUF 1.513 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.27 · 7 PDB
Residue 24: an α-helix

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-val24leu (accessed [today's date]).

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