Is CCL5 p.Ser58Phe (c.173C>T) pathogenic?

CCL5 p.Ser58Phe (c.173C>T) is classified Uncertain significance in CCL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-16). AlphaMissense: ambiguous (0.4363); Very rare (popmax 8.48e-05%, nfe).

How common is CCL5 p.Ser58Phe (c.173C>T) in the general population?

CCL5 p.Ser58Phe (c.173C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CCL5 p.Ser58Phe (c.173C>T)?

AlphaMissense predicts ambiguous (score 0.4363) — an in-silico prediction, not a clinical call.

CCL5 p.Ser58Phe

c.173C>T · VCV3829009

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4363 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4363	ambiguous
REVEL	0.198	benign-leaning
SaProt	LLR -10.83	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 1.7, phastCons 1
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,502 alleles

Overall 6.84e-05% 1/1,461,300 alleles · very 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: CCL5
Protein: p.Ser58Phe
Coding: c.173C>T
MANE Select: NM_002985
Type: single nucleotide variant
Location: chr17:35878543 (GRCh38)
Gene constraint: LOEUF 1.387 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 89.51 · 23 PDB
Residue 58: a β-strand; a disulfide bond

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

Similar variants

CCL5 p.Arg40His Uncertain significance ★ ⚠ same type
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.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-ser58phe (accessed [today's date]).

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