Is CCL7 p.Pro44Arg (c.131C>G) pathogenic?

CCL7 p.Pro44Arg (c.131C>G) is classified Uncertain significance in CCL7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-18). AlphaMissense: likely benign (0.3327); Very rare (popmax 0.00446%, eas).

How common is CCL7 p.Pro44Arg (c.131C>G) in the general population?

CCL7 p.Pro44Arg (c.131C>G) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about CCL7 p.Pro44Arg (c.131C>G)?

AlphaMissense predicts likely benign (score 0.3327) — an in-silico prediction, not a clinical call.

CCL7 p.Pro44Arg

c.131C>G · rs371185605 · VCV2516893

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3327 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3327	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -10.65	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.23	donor gain · deltas
Constraint at this position
Conservation	phyloP -0.91	GERP -2.4
Regional constraint	o/e 1.18	unconstrained · MANE · 1,508 bp · p 0.056 · regional, not allelic
Overall
CADD	16.06	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 0.00446% East Asian · 2/44,886 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000248% 4/1,614,006 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,443
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	8.47e-05%	1,180,027

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: CCL7
Protein: p.Pro44Arg
Coding: c.131C>G
MANE Select: NM_006273
dbSNP: rs371185605
Type: single nucleotide variant
Location: chr17:34271200 (GRCh38)
Gene constraint: LOEUF 1.727 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.93 · 10 PDB
Residue 44: an α-helix; a disulfide bond

Full CCL7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCL7 p.Ala63Thr Uncertain significance ★ ⚠ same type
CCL7 p.Ala76Asp Uncertain significance ★ ⚠ same type
CCL7 p.Ala76Thr Uncertain significance ★ ⚠ same type
CCL7 p.Asp71Glu Uncertain significance ★ ⚠ same type
CCL7 p.Asp85His Uncertain significance ★ ⚠ same type
CCL7 p.Phe38Leu Uncertain significance ★ ⚠ same type
CCL7 p.Thr94Ile Uncertain significance ★ ⚠ same type
CCL7 p.Thr96Ile 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/ccl7-p-pro44arg (accessed [today's date]).

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