Is CCR4 p.Ile15Val (c.43A>G) pathogenic?

CCR4 p.Ile15Val (c.43A>G) is classified Uncertain significance in CCR4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-10). AlphaMissense: likely benign (0.0734); Ultra-rare (popmax 0.0913%, eas).

How common is CCR4 p.Ile15Val (c.43A>G) in the general population?

CCR4 p.Ile15Val (c.43A>G) is ultra-rare (popmax 0.0913%, eas) (gnomAD).

What do computational predictors say about CCR4 p.Ile15Val (c.43A>G)?

AlphaMissense predicts likely benign (score 0.0734) — an in-silico prediction, not a clinical call.

CCR4 p.Ile15Val

c.43A>G · rs767703983 · VCV2470777

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0734 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0913%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0734	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -6.19	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 -0.93	GERP -2.8
Overall
CADD	0.264	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 0.0913% East Asian · 41/44,898 alleles

Filtering AF 0.0692% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0614%

Overall 0.00297% 48/1,613,838 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0913%	1,095
Remaining individualsnot grpmax-eligible	0.008%	12,496
European (non-Finnish)	0.00017%	589,939

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: CCR4
Protein: p.Ile15Val
Coding: c.43A>G
MANE Select: NM_001370472 · reported on NM_005508
dbSNP: rs767703983
Type: single nucleotide variant
Location: chr3:32953465 (GRCh38)
Structure: AlphaFold pLDDT 89.51 · 1 PDB

Full CCR4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCR4 p.Ala246Thr Uncertain significance ★ ⚠ same type
CCR4 p.Ala246Val Uncertain significance ★ ⚠ same type
CCR4 p.Arg147Trp Uncertain significance ★ ⚠ same type
CCR4 p.Cys178Arg Uncertain significance ★ ⚠ same type
CCR4 p.Cys329Gly Uncertain significance ★ ⚠ same type
CCR4 p.Gln230Lys Uncertain significance ★ ⚠ same type
CCR4 p.His357Arg Uncertain significance ★ ⚠ same type
CCR4 p.Ile208Met 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/ccr4-p-ile15val (accessed [today's date]).

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