Is CCR5 p.Phe299fs (c.894del) pathogenic?

CCR5 p.Phe299fs (c.894del) is classified Benign in CCR5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 1997-07-01). Rare (popmax 0.94%, eas); Associated with CCR5 POLYMORPHISM, ORIENTAL 1.

What condition is associated with CCR5 p.Phe299fs (c.894del)?

CCR5 p.Phe299fs (c.894del) is associated with CCR5 POLYMORPHISM, ORIENTAL 1 (ClinVar).

How common is CCR5 p.Phe299fs (c.894del) in the general population?

CCR5 p.Phe299fs (c.894del) is rare (popmax 0.94%, eas) (gnomAD).

CCR5 p.Phe299fs

c.894del · rs796065305 · VCV8185

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.94%, eas)

Conditions

CCR5 POLYMORPHISM, ORIENTAL 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (2 of 2) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Overall
CADD	27.5	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.94% East Asian · 422/44,884 alleles

Filtering AF 0.866% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.837%

Overall 0.027% 435/1,613,942 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.94%	106
Remaining individualsnot grpmax-eligible	0.0192%	5,208
European (non-Finnish)	8.48e-05%	1,179,830

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.Phe299fs
Coding: c.894del
MANE Select: NM_001394783
dbSNP: rs796065305
Type: Deletion
Location: chr3:46373795 (GRCh38)
Gene constraint: LOEUF 1.592 · pLI 0.18 (gnomAD)
Structure: AlphaFold pLDDT 85.41 · 26 PDB
Residue 299: an α-helix

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

Disease context

CCR5 POLYMORPHISM, ORIENTAL 1

Similar variants

CCR5 p.Thr239Ala Uncertain significance ★ ⚠ same condition
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.Ser185fs Benign ★ 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-phe299fs (accessed [today's date]).

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