Is CCR5 p.Ser63Cys (c.187A>T) pathogenic?

CCR5 p.Ser63Cys (c.187A>T) is classified Uncertain significance in CCR5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2020-11-09). AlphaMissense: likely benign (0.1795); Rare (popmax 0.181%, mid); Associated with West Nile virus, susceptibility to.

What condition is associated with CCR5 p.Ser63Cys (c.187A>T)?

CCR5 p.Ser63Cys (c.187A>T) is associated with West Nile virus, susceptibility to, susceptibility to HIV infection, hepatitis C virus, susceptibility to (ClinVar).

How common is CCR5 p.Ser63Cys (c.187A>T) in the general population?

CCR5 p.Ser63Cys (c.187A>T) is rare (popmax 0.181%, mid) (gnomAD).

What do computational predictors say about CCR5 p.Ser63Cys (c.187A>T)?

AlphaMissense predicts likely benign (score 0.1795) — an in-silico prediction, not a clinical call.

CCR5 p.Ser63Cys

c.187A>T · rs142829420 · VCV992556

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1795 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.181%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

West Nile virus, susceptibility to

Computational evidence

Protein change
AlphaMissense	0.1795	likely benign
REVEL	0.218	benign-leaning
SaProt	LLR -10.78	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	GERP 2.2, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 1,055 bp · p 0.04 · regional, not allelic
Overall
CADD	19.56	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 0.181% Middle Eastern · 11/6,062 alleles

Filtering AF 0.128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.118%

Overall 0.0891% 1,438/1,614,204 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.181%	551
Admixed American	0.153%	652
Remaining individualsnot grpmax-eligible	0.114%	880
European (non-Finnish)	0.1%	1,000
South Asian	0.0802%	1,248
African / African-American	0.0133%	7,505
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608

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: CCR5
Protein: p.Ser63Cys
Coding: c.187A>T
MANE Select: NM_001394783
dbSNP: rs142829420
Type: single nucleotide variant
Location: chr3:46373089 (GRCh38)
Gene constraint: LOEUF 1.592 · pLI 0.18 (gnomAD)
Structure: AlphaFold pLDDT 85.41 · 26 PDB
Residue 63: a disulfide bond

Full CCR5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

West Nile virus, susceptibility to — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: susceptibility to HIV infection hepatitis C virus, susceptibility to type 1 diabetes mellitus 22

Similar variants

CCR5 p.Ser185fs Benign ★ same condition
CCR5 p.Ala298Asp Uncertain significance ★ ⚠ same type
CCR5 p.Ala91Val Uncertain significance ★ ⚠ same type
CCR5 p.Ala92Thr Uncertain significance ★ ⚠ same type
CCR5 p.Arg168Gly Uncertain significance ★ ⚠ same type
CCR5 p.Arg274Lys Uncertain significance ★ ⚠ same type
CCR5 p.Arg31His Uncertain significance ★ ⚠ same type
CCR5 p.Arg341Gln 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/ccr5-p-ser63cys (accessed [today's date]).

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