Is CCL2 p.Cys35= (c.105T>C) pathogenic?

CCL2 p.Cys35= (c.105T>C) is classified Benign in CCL2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-17). Common (popmax 67%, afr) — too common for a highly-penetrant pathogenic allele; Associated with CCL2-related disorder.

What condition is associated with CCL2 p.Cys35= (c.105T>C)?

CCL2 p.Cys35= (c.105T>C) is associated with CCL2-related disorder (ClinVar).

CCL2 p.Cys35=

Q: How common is CCL2 p.Cys35= (c.105T>C) in the general population?

CCL2 p.Cys35= (c.105T>C) is common (popmax 67%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.105T>C · rs4586 · VCV3059105

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 67%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

CCL2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -0.79, phastCons 1
Overall
CADD	7.629	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 67% African / African-American · 50,137/74,858 alleles

Filtering AF 66.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 66.3%

Overall 39.6% 637,758/1,609,614 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	67%	1
East Asian	60.5%	2
Admixed American	58.2%	2
South Asian	45.3%	2
Middle Eastern	42.8%	2
Finnishnot grpmax-eligible	40.8%	2
Remaining individualsnot grpmax-eligible	40.5%	2
European (non-Finnish)	35.7%	3
Ashkenazi Jewishnot grpmax-eligible	35.4%	3
Amishnot grpmax-eligible	22.1%	5

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.Cys35=
Coding: c.105T>C
MANE Select: NM_002982
dbSNP: rs4586
Type: single nucleotide variant
Location: chr17:34256250 (GRCh38)
Gene constraint: LOEUF 1.84 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 87.51 · 14 PDB
Residue 35: a disulfide bond

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

Disease context

CCL2-related disorder

Similar variants

CCL2 p.Leu48= Likely benign same condition
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.Pro97Leu Uncertain significance ★ ⚠ same type
CCL2 p.Thr55Ser 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/ccl2-p-cys35 (accessed [today's date]).

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