Is CCR8 p.Ile196Ser (c.587T>G) pathogenic?

CCR8 p.Ile196Ser (c.587T>G) is classified Uncertain significance in CCR8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-02). AlphaMissense: ambiguous (0.4326); Ultra-rare (popmax 0.048%, afr).

How common is CCR8 p.Ile196Ser (c.587T>G) in the general population?

CCR8 p.Ile196Ser (c.587T>G) is ultra-rare (popmax 0.048%, afr) (gnomAD).

What do computational predictors say about CCR8 p.Ile196Ser (c.587T>G)?

AlphaMissense predicts ambiguous (score 0.4326) — an in-silico prediction, not a clinical call.

CCR8 p.Ile196Ser

c.587T>G · VCV3264645

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4326 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.048%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4326	ambiguous
REVEL	0.127	moderately benign-leaning
SaProt	LLR -9.29	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	phastCons 0.93
Regional constraint	o/e 0.86	unconstrained · MANE · 1,064 bp · p 0.0036 · regional, not allelic
Overall
CADD	20.5	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 0.048% African / African-American · 36/75,042 alleles

Filtering AF 0.0356% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0313%

Overall 0.00279% 45/1,614,052 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.048%	2,085
Admixed American	0.00833%	12,001
Remaining individualsnot grpmax-eligible	0.0048%	20,836
European (non-Finnish)	8.48e-05%	1,179,920

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.Ile196Ser
Coding: c.587T>G
MANE Select: NM_005201
Type: single nucleotide variant
Location: chr3:39332918 (GRCh38)
Gene constraint: LOEUF 1.95 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 82.21 · 6 PDB
Residue 196: a disulfide bond

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-ile196ser (accessed [today's date]).

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