Is CCR8 p.Val85Phe (c.253G>T) pathogenic?

CCR8 p.Val85Phe (c.253G>T) is classified Uncertain significance in CCR8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-09). AlphaMissense: likely pathogenic (0.702); Ultra-rare (popmax 0.045%, amr).

How common is CCR8 p.Val85Phe (c.253G>T) in the general population?

CCR8 p.Val85Phe (c.253G>T) is ultra-rare (popmax 0.045%, amr) (gnomAD).

What do computational predictors say about CCR8 p.Val85Phe (c.253G>T)?

AlphaMissense predicts likely pathogenic (score 0.702) — an in-silico prediction, not a clinical call.

CCR8 p.Val85Phe

c.253G>T · rs189767921 · VCV2390268

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.702 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.045%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.702	likely pathogenic
REVEL	0.342	indeterminate
SaProt	LLR -10.95	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.2	phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 1,064 bp · p 0.0036 · regional, not allelic
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.045% Admixed American · 27/60,012 alleles

Filtering AF 0.0317% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0273%

Overall 0.00192% 31/1,614,116 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.045%	2,223
Remaining individualsnot grpmax-eligible	0.0048%	20,835
African / African-American	0.00133%	75,032

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: CCR8
Protein: p.Val85Phe
Coding: c.253G>T
MANE Select: NM_005201
dbSNP: rs189767921
Type: single nucleotide variant
Location: chr3:39332584 (GRCh38)
Gene constraint: LOEUF 1.95 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 82.21 · 6 PDB
Residue 85: a disulfide bond; an α-helix

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

Similar variants

CCR8 p.Ala175Val Uncertain significance ★ ⚠ same type
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

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-val85phe (accessed [today's date]).

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