Is CCR4 p.Pro343Ser (c.1027C>T) pathogenic?

CCR4 p.Pro343Ser (c.1027C>T) is classified Uncertain significance in CCR4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-03). AlphaMissense: likely benign (0.0737); Very rare (popmax 8.57e-05%, nfe).

How common is CCR4 p.Pro343Ser (c.1027C>T) in the general population?

CCR4 p.Pro343Ser (c.1027C>T) is very rare (popmax 8.57e-05%, nfe) (gnomAD).

What do computational predictors say about CCR4 p.Pro343Ser (c.1027C>T)?

AlphaMissense predicts likely benign (score 0.0737) — an in-silico prediction, not a clinical call.

CCR4 p.Pro343Ser

c.1027C>T · VCV3829216

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0737 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.57e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0737	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -4.24	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 -0.24	GERP -2.5
Overall
CADD	1.708	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 8.57e-05% European (non-Finnish) · 1/1,166,834 alleles

Overall 7e-05% 1/1,428,140 alleles · very rare

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.Pro343Ser
Coding: c.1027C>T
MANE Select: NM_001370472 · reported on NM_005508
Type: single nucleotide variant
Location: chr3:32954449 (GRCh38)
Structure: AlphaFold pLDDT 89.51 · 1 PDB
Residue 343: the 'nuclease domain' region

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.Ile15Val 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-pro343ser (accessed [today's date]).

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