Is CCL5 p.Arg40His (c.119G>A) pathogenic?

CCL5 p.Arg40His (c.119G>A) is classified Uncertain significance in CCL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-05). AlphaMissense: likely benign (0.1593); Ultra-rare (popmax 0.0668%, afr).

How common is CCL5 p.Arg40His (c.119G>A) in the general population?

CCL5 p.Arg40His (c.119G>A) is ultra-rare (popmax 0.0668%, afr) (gnomAD).

What do computational predictors say about CCL5 p.Arg40His (c.119G>A)?

AlphaMissense predicts likely benign (score 0.1593) — an in-silico prediction, not a clinical call.

CCL5 p.Arg40His

c.119G>A · rs138511589 · VCV2380266

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1593 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0668%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1593	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -8.44	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 0.81	GERP 1.7, phastCons 0.16
Overall
CADD	22.0	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 0.0668% African / African-American · 50/74,906 alleles

Filtering AF 0.052% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0467%

Overall 0.00471% 76/1,613,460 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0668%	1,498
Admixed American	0.0117%	8,562
Remaining individualsnot grpmax-eligible	0.0096%	10,414
East Asian	0.00223%	44,852
South Asian	0.0022%	45,497
European (non-Finnish)	0.000848%	117,976

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: CCL5
Protein: p.Arg40His
Coding: c.119G>A
MANE Select: NM_002985
dbSNP: rs138511589
Type: single nucleotide variant
Location: chr17:35878597 (GRCh38)
Gene constraint: LOEUF 1.387 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 89.51 · 23 PDB
Residue 40: a β-strand; a disulfide bond

Full CCL5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCL5 p.Arg70His Uncertain significance ★ ⚠ same type
CCL5 p.Arg82Gln Uncertain significance ★ ⚠ same type
CCL5 p.Cys33Arg Uncertain significance ★ ⚠ same type
CCL5 p.Lys68Arg Uncertain significance ★ ⚠ same type
CCL5 p.Ser28Leu Uncertain significance ★ ⚠ same type
CCL5 p.Ser58Phe Uncertain significance ★ ⚠ same type
CCL5 p.Thr30Ala Uncertain significance ★ ⚠ same type
CCL5 p.Val72Met 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/ccl5-p-arg40his (accessed [today's date]).

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