Is CCR5 p.Thr239Ala (c.715A>G) pathogenic?

CCR5 p.Thr239Ala (c.715A>G) is classified Uncertain significance in CCR5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-04). AlphaMissense: likely benign (0.0796); Ultra-rare (popmax 0.0165%, mid); Associated with CCR5-related disorder.

What condition is associated with CCR5 p.Thr239Ala (c.715A>G)?

CCR5 p.Thr239Ala (c.715A>G) is associated with CCR5-related disorder (ClinVar).

How common is CCR5 p.Thr239Ala (c.715A>G) in the general population?

CCR5 p.Thr239Ala (c.715A>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CCR5 p.Thr239Ala (c.715A>G)?

AlphaMissense predicts likely benign (score 0.0796) — an in-silico prediction, not a clinical call.

CCR5 p.Thr239Ala

c.715A>G · rs1575279854 · VCV2634364

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0796 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CCR5-related disorder

Computational evidence

Protein change
AlphaMissense	0.0796	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -9.35	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 0.72	GERP -3.7
Regional constraint	o/e 1.10	unconstrained · MANE · 1,055 bp · p 0.04 · regional, not allelic
Overall
CADD	7.476	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

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Overall 0.000137% 2/1,461,818 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
East Asian	0.00223%	44,872

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.Thr239Ala
Coding: c.715A>G
MANE Select: NM_001394783
dbSNP: rs1575279854
Type: single nucleotide variant
Location: chr3:46373617 (GRCh38)
Gene constraint: LOEUF 1.592 · pLI 0.18 (gnomAD)
Structure: AlphaFold pLDDT 85.41 · 26 PDB
Residue 239: an α-helix; a disulfide bond; a UniProt-annotated variant site (in inccr5-71a)

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

Disease context

CCR5-related disorder

Similar variants

CCR5 p.Gly106Arg Likely benign same condition
CCR5 p.Ile23= Likely benign same condition
CCR5 p.Phe247= Likely benign same condition
CCR5 p.Thr141= Likely benign same condition
CCR5 p.Phe299fs Benign same condition
CCR5 p.Ser63Cys Uncertain significance ★★ ⚠ same type
CCR5 p.Ala298Asp Uncertain significance ★ ⚠ same type
CCR5 p.Ala91Val 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-thr239ala (accessed [today's date]).

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