Is COMMD10 p.Ile75Val (c.223A>G) pathogenic?

COMMD10 p.Ile75Val (c.223A>G) is classified Uncertain significance in COMMD10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-18). AlphaMissense: likely benign (0.0621); Ultra-rare (popmax 0.0241%, afr).

How common is COMMD10 p.Ile75Val (c.223A>G) in the general population?

COMMD10 p.Ile75Val (c.223A>G) is ultra-rare (popmax 0.0241%, afr) (gnomAD).

What do computational predictors say about COMMD10 p.Ile75Val (c.223A>G)?

AlphaMissense predicts likely benign (score 0.0621) — an in-silico prediction, not a clinical call.

COMMD10 p.Ile75Val

c.223A>G · VCV4655784

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0621 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0241%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0621	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -5.40	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 3	GERP -0.66, phastCons 1
Regional constraint	o/e 1.33	unconstrained · MANE · 207 kb · p 5.3e-07 · regional, not allelic
Overall
CADD	15.8	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

Grpmax group 0.0241% African / African-American · 18/74,604 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0129%

Overall 0.0015% 24/1,599,620 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0241%	4,145
Middle Eastern	0.0167%	6,006
South Asian	0.00223%	44,765
European (non-Finnish)	0.000257%	389,809

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.Ile75Val
Coding: c.223A>G
MANE Select: NM_016144
Type: single nucleotide variant
Location: chr5:116091169 (GRCh38)
Gene constraint: LOEUF 1.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.19 · 6 PDB
Residue 75: an α-helix

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

Similar variants

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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-ile75val (accessed [today's date]).

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