Is CCL2 p.Pro97Leu (c.290C>T) pathogenic?

CCL2 p.Pro97Leu (c.290C>T) is classified Uncertain significance in CCL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-05). AlphaMissense: likely benign (0.0936); Ultra-rare (popmax 0.0383%, nfe).

How common is CCL2 p.Pro97Leu (c.290C>T) in the general population?

CCL2 p.Pro97Leu (c.290C>T) is ultra-rare (popmax 0.0383%, nfe) (gnomAD).

What do computational predictors say about CCL2 p.Pro97Leu (c.290C>T)?

AlphaMissense predicts likely benign (score 0.0936) — an in-silico prediction, not a clinical call.

CCL2 p.Pro97Leu

c.290C>T · VCV3487269

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0936 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0383%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0936	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -10.46	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.89	GERP -2.5
Regional constraint	o/e 0.75	unconstrained · MANE · 1,474 bp · p 0.0055 · regional, not allelic
Overall
CADD	11.53	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 0.0383% European (non-Finnish) · 451/1,177,848 alleles

Filtering AF 0.0353% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0342%

Overall 0.0296% 477/1,611,514 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0383%	2,612
Remaining individualsnot grpmax-eligible	0.0289%	3,466
Admixed American	0.005%	19,987
East Asian	0.00446%	22,442
African / African-American	0.00401%	24,953

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: CCL2
Protein: p.Pro97Leu
Coding: c.290C>T
MANE Select: NM_002982
Type: single nucleotide variant
Location: chr17:34256817 (GRCh38)
Gene constraint: LOEUF 1.84 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 87.51 · 14 PDB

Full CCL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCL2 p.Ala15Pro Uncertain significance ★ ⚠ same type
CCL2 p.Ala49Val Uncertain significance ★ ⚠ same type
CCL2 p.Asp85Tyr Uncertain significance ★ ⚠ same type
CCL2 p.Met87Val Uncertain significance ★ ⚠ same type
CCL2 p.Thr55Ser Uncertain significance ★ ⚠ same type
CCL2 p.Cys35= Benign same type
CCL2 p.Leu48= 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/ccl2-p-pro97leu (accessed [today's date]).

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