Is CCR5 p.Arg341Gln (c.1022G>A) pathogenic?

CCR5 p.Arg341Gln (c.1022G>A) is classified Uncertain significance in CCR5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely benign (0.0881); Ultra-rare (popmax 0.0122%, amr).

How common is CCR5 p.Arg341Gln (c.1022G>A) in the general population?

CCR5 p.Arg341Gln (c.1022G>A) is ultra-rare (popmax 0.0122%, amr) (gnomAD).

What do computational predictors say about CCR5 p.Arg341Gln (c.1022G>A)?

AlphaMissense predicts likely benign (score 0.0881) — an in-silico prediction, not a clinical call.

CCR5 p.Arg341Gln

c.1022G>A · VCV4222280

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0881 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0122%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0881	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -5.99	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 3	GERP 0.82, phastCons 0.43
Regional constraint	o/e 1.10	unconstrained · MANE · 1,055 bp · p 0.04 · regional, not allelic
Overall
CADD	19.75	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 0.0122% Admixed American · 7/57,424 alleles

Filtering AF 0.00565% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00404%

Overall 0.00214% 34/1,587,024 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0122%	8,203
African / African-American	0.00404%	24,725
South Asian	0.00228%	43,890
East Asian	0.00224%	44,606
European (non-Finnish)	0.00172%	58,184
Remaining individualsnot grpmax-eligible	0.00163%	61,216

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.Arg341Gln
Coding: c.1022G>A
MANE Select: NM_001394783
Type: single nucleotide variant
Location: chr3:46373924 (GRCh38)
Gene constraint: LOEUF 1.592 · pLI 0.18 (gnomAD)
Structure: AlphaFold pLDDT 85.41 · 26 PDB
Residue 341: a β-strand

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.Glu18Lys 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-arg341gln (accessed [today's date]).

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