Is CCR5 p.Ile23= (c.69C>A) pathogenic?

CCR5 p.Ile23= (c.69C>A) is classified Likely benign in CCR5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-27). Ultra-rare (popmax 0.0187%, sas); Associated with CCR5-related disorder.

What condition is associated with CCR5 p.Ile23= (c.69C>A)?

CCR5 p.Ile23= (c.69C>A) is associated with CCR5-related disorder (ClinVar).

How common is CCR5 p.Ile23= (c.69C>A) in the general population?

CCR5 p.Ile23= (c.69C>A) is ultra-rare (popmax 0.0187%, sas) (gnomAD).

CCR5 p.Ile23=

c.69C>A · rs763103073 · VCV3058502

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, sas)

Conditions

CCR5-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.005	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.2	GERP -4.4
Overall
CADD	0.591	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% South Asian · 17/90,964 alleles

Filtering AF 0.0119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00977%

Overall 0.00116% 17/1,461,086 alleles · ultra-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: CCR5
Protein: p.Ile23=
Coding: c.69C>A
MANE Select: NM_001394783
dbSNP: rs763103073
Type: single nucleotide variant
Location: chr3:46372971 (GRCh38)
Gene constraint: LOEUF 1.592 · pLI 0.18 (gnomAD)
Structure: AlphaFold pLDDT 85.41 · 26 PDB
Residue 23: a disulfide bond; an α-helix

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

Disease context

CCR5-related disorder

Similar variants

CCR5 p.Thr239Ala Uncertain significance ★ ⚠ same condition
CCR5 p.Gly106Arg 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-ile23 (accessed [today's date]).

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