Is CCR1 p.Pro39Thr (c.115C>A) pathogenic?

CCR1 p.Pro39Thr (c.115C>A) is classified Uncertain significance in CCR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-15). AlphaMissense: likely benign (0.1319); Very rare (popmax 8.47e-05%, nfe).

How common is CCR1 p.Pro39Thr (c.115C>A) in the general population?

CCR1 p.Pro39Thr (c.115C>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CCR1 p.Pro39Thr (c.115C>A)?

AlphaMissense predicts likely benign (score 0.1319) — an in-silico prediction, not a clinical call.

CCR1 p.Pro39Thr

c.115C>A · VCV4650189

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1319 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1319	likely benign
REVEL	0.164	moderately benign-leaning
SaProt	LLR -9.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP 1.4, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 1,064 bp · p 3.5e-05 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 8.47e-05% European (non-Finnish) · 1/1,180,008 alleles

Overall 6.84e-05% 1/1,461,862 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: CCR1
Protein: p.Pro39Thr
Coding: c.115C>A
MANE Select: NM_001295
Type: single nucleotide variant
Location: chr3:46204199 (GRCh38)
Gene constraint: LOEUF 1.931 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 83.49 · 3 PDB
Residue 39: a disulfide bond; an α-helix

Full CCR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCR1 p.Ala159Val Likely benign ★★ same type
CCR1 p.Leu127= Benign ★★ same type
CCR1 p.Leu54= Benign/Likely benign ★★ same type
CCR1 p.Ter356= Benign ★★ same type
CCR1 p.Thr146= Likely benign ★★ same type
CCR1 p.Tyr291His Benign ★★ same type
CCR1 p.Tyr301= Benign/Likely benign ★★ same type
CCR1 p.Ala159Ser 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/ccr1-p-pro39thr (accessed [today's date]).

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