Is CCR8 p.Pro331Ser (c.991C>T) pathogenic?

CCR8 p.Pro331Ser (c.991C>T) is classified Likely benign in CCR8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-04). AlphaMissense: likely benign (0.0987); Very rare (popmax 0.000593%, nfe).

How common is CCR8 p.Pro331Ser (c.991C>T) in the general population?

CCR8 p.Pro331Ser (c.991C>T) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about CCR8 p.Pro331Ser (c.991C>T)?

AlphaMissense predicts likely benign (score 0.0987) — an in-silico prediction, not a clinical call.

CCR8 p.Pro331Ser

c.991C>T · VCV3487596

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0987 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0987	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -6.08	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 -1.2	GERP -4.2
Regional constraint	o/e 0.86	unconstrained · MANE · 1,064 bp · p 0.0036 · regional, not allelic
Overall
CADD	0.357	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000593% European (non-Finnish) · 7/1,179,970 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000434% 7/1,613,886 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: CCR8
Protein: p.Pro331Ser
Coding: c.991C>T
MANE Select: NM_005201
Type: single nucleotide variant
Location: chr3:39333322 (GRCh38)
Gene constraint: LOEUF 1.95 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 82.21 · 6 PDB

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

Similar variants

CCR8 p.Pro331Leu Uncertain significance ★ ⚠ same residue
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

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-pro331ser (accessed [today's date]).

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