Is CCR5 p.Phe247= (c.741C>T) pathogenic?

CCR5 p.Phe247= (c.741C>T) is classified Likely benign in CCR5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-01). Ultra-rare (popmax 0.0164%, mid); Associated with CCR5-related disorder.

What condition is associated with CCR5 p.Phe247= (c.741C>T)?

CCR5 p.Phe247= (c.741C>T) is associated with CCR5-related disorder (ClinVar).

How common is CCR5 p.Phe247= (c.741C>T) in the general population?

CCR5 p.Phe247= (c.741C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

CCR5 p.Phe247=

c.741C>T · rs141139165 · VCV3057661

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

CCR5-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 0.84, phastCons 1
Overall
CADD	11.26	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00347% 56/1,614,000 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0128%	7,811
Admixed American	0.01%	10,002
European (non-Finnish)	0.00339%	29,500
Finnishnot grpmax-eligible	0.00156%	64,014

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.Phe247=
Coding: c.741C>T
MANE Select: NM_001394783
dbSNP: rs141139165
Type: single nucleotide variant
Location: chr3:46373643 (GRCh38)
Gene constraint: LOEUF 1.592 · pLI 0.18 (gnomAD)
Structure: AlphaFold pLDDT 85.41 · 26 PDB
Residue 247: an α-helix; a disulfide bond

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

Disease context

CCR5-related disorder

Similar variants

CCR5 p.Phe247Ser Uncertain significance ★ ⚠ same residue
CCR5 p.Thr239Ala Uncertain significance ★ ⚠ same condition
CCR5 p.Gly106Arg Likely benign same condition
CCR5 p.Ile23= 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

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-phe247 (accessed [today's date]).

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