Is CCR5 p.Thr99Ser (c.295A>T) pathogenic?

CCR5 p.Thr99Ser (c.295A>T) is classified Uncertain significance in CCR5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-06). AlphaMissense: likely benign (0.1016); Absent from gnomAD v4.1.

How common is CCR5 p.Thr99Ser (c.295A>T) in the general population?

CCR5 p.Thr99Ser (c.295A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCR5 p.Thr99Ser (c.295A>T)?

AlphaMissense predicts likely benign (score 0.1016) — an in-silico prediction, not a clinical call.

CCR5 p.Thr99Ser

c.295A>T · rs1701690973 · VCV2333544

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1016 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1016	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -7.28	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 -1.8	GERP -4.4
Regional constraint	o/e 1.10	unconstrained · MANE · 1,055 bp · p 0.04 · regional, not allelic
Overall
CADD	0.078	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: CCR5
Protein: p.Thr99Ser
Coding: c.295A>T
MANE Select: NM_001394783
dbSNP: rs1701690973
Type: single nucleotide variant
Location: chr3:46373197 (GRCh38)
Gene constraint: LOEUF 1.592 · pLI 0.18 (gnomAD)
Structure: AlphaFold pLDDT 85.41 · 26 PDB
Residue 99: a disulfide bond; an α-helix

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

Similar variants

CCR5 p.Ser63Cys Uncertain significance ★★ ⚠ same type
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-thr99ser (accessed [today's date]).

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