Is CCL1 p.Cys57Phe (c.170G>T) pathogenic?

CCL1 p.Cys57Phe (c.170G>T) is classified Uncertain significance in CCL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-07). AlphaMissense: likely pathogenic (0.7966); Very rare (popmax 8.49e-05%, nfe).

How common is CCL1 p.Cys57Phe (c.170G>T) in the general population?

CCL1 p.Cys57Phe (c.170G>T) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about CCL1 p.Cys57Phe (c.170G>T)?

AlphaMissense predicts likely pathogenic (score 0.7966) — an in-silico prediction, not a clinical call.

CCL1 p.Cys57Phe

c.170G>T · VCV3487252

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7966 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7966	likely pathogenic · top 9% in CCL1
REVEL	0.61	indeterminate
SaProt	LLR -11.49	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 2,599 bp · p 0.73 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.49e-05% European (non-Finnish) · 1/1,177,388 alleles

Overall 6.85e-05% 1/1,458,838 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: CCL1
Protein: p.Cys57Phe
Coding: c.170G>T
MANE Select: NM_002981
Type: single nucleotide variant
Location: chr17:34361803 (GRCh38)
Gene constraint: LOEUF 1.948 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.36 · 4 PDB
Residue 57: an α-helix; a disulfide bond

Full CCL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCL1 p.Arg89Thr Uncertain significance ★ ⚠ same type
CCL1 p.Asp20Val Uncertain significance ★ ⚠ same type
CCL1 p.Lys65Arg Uncertain significance ★ ⚠ same type
CCL1 p.Lys94Arg Uncertain significance ★ ⚠ same type
CCL1 p.Pro92Leu Likely 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/ccl1-p-cys57phe (accessed [today's date]).

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