Is CCR2 p.Arg238Ser (c.714G>T) pathogenic?

CCR2 p.Arg238Ser (c.714G>T) is classified Uncertain significance in CCR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-03). AlphaMissense: likely pathogenic (0.5896); Very rare (popmax 8.47e-05%, nfe).

How common is CCR2 p.Arg238Ser (c.714G>T) in the general population?

CCR2 p.Arg238Ser (c.714G>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CCR2 p.Arg238Ser (c.714G>T)?

AlphaMissense predicts likely pathogenic (score 0.5896) — an in-silico prediction, not a clinical call.

CCR2 p.Arg238Ser

c.714G>T · VCV3997769

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5896 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5896	likely pathogenic
REVEL	0.073	moderately benign-leaning
SaProt	LLR -4.15	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 0.23, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 1,079 bp · p 0.13 · regional, not allelic
Overall
CADD	19.16	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 8.47e-05% European (non-Finnish) · 1/1,180,024 alleles

Overall 6.2e-05% 1/1,614,164 alleles · very rare exomes 1/1,461,870 · genomes 0/152,294 · joint denominator

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: CCR2
Protein: p.Arg238Ser
Coding: c.714G>T
MANE Select: NM_001123396
Type: single nucleotide variant
Location: chr3:46358241 (GRCh38)
Gene constraint: LOEUF 1.825 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 78.28 · 7 PDB
Residue 238: an α-helix

Full CCR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCR2 c.*1179G>A Uncertain significance ★★ ⚠ same type
CCR2 p.Val52= Benign ★★ same type
CCR2 p.Arg196Ter Likely pathogenic ★ same type
CCR2 c.*1068C>A Uncertain significance ★ ⚠ same type
CCR2 c.*1141C>A Uncertain significance ★ ⚠ same type
CCR2 c.*1168A>G Uncertain significance ★ ⚠ same type
CCR2 c.*1176C>G Uncertain significance ★ ⚠ same type
CCR2 c.*1198A>G 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/ccr2-p-arg238ser (accessed [today's date]).

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