Is CCR8 p.Ala175Val (c.524C>T) pathogenic?

CCR8 p.Ala175Val (c.524C>T) is classified Uncertain significance in CCR8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-21). AlphaMissense: likely benign (0.1039); Absent from gnomAD v4.1.

How common is CCR8 p.Ala175Val (c.524C>T) in the general population?

CCR8 p.Ala175Val (c.524C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCR8 p.Ala175Val (c.524C>T)?

AlphaMissense predicts likely benign (score 0.1039) — an in-silico prediction, not a clinical call.

CCR8 p.Ala175Val

c.524C>T · VCV3997794

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1039 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1039	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -4.63	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 0.67
Regional constraint	o/e 0.86	unconstrained · MANE · 1,064 bp · p 0.0036 · regional, not allelic
Overall
CADD	12.13	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: CCR8
Protein: p.Ala175Val
Coding: c.524C>T
MANE Select: NM_005201
Type: single nucleotide variant
Location: chr3:39332855 (GRCh38)
Gene constraint: LOEUF 1.95 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 82.21 · 6 PDB
Residue 175: a disulfide bond; a β-strand

Full CCR8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCR8 p.Arg347Cys Uncertain significance ★ ⚠ same type
CCR8 p.Asn199Ser Uncertain significance ★ ⚠ same type
CCR8 p.Asp130Asn Uncertain significance ★ ⚠ same type
CCR8 p.Asp270Glu Uncertain significance ★ ⚠ same type
CCR8 p.Cys341Gly Uncertain significance ★ ⚠ same type
CCR8 p.Glu333Lys Uncertain significance ★ ⚠ same type
CCR8 p.His344Asn Uncertain significance ★ ⚠ same type
CCR8 p.Ile124Val 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/ccr8-p-ala175val (accessed [today's date]).

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