Is CCR3 p.Phe248Val (c.742T>G) pathogenic?

CCR3 p.Phe248Val (c.742T>G) is classified Uncertain significance in CCR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely pathogenic (0.6477); Rare (popmax 0.124%, afr).

How common is CCR3 p.Phe248Val (c.742T>G) in the general population?

CCR3 p.Phe248Val (c.742T>G) is rare (popmax 0.124%, afr) (gnomAD).

What do computational predictors say about CCR3 p.Phe248Val (c.742T>G)?

AlphaMissense predicts likely pathogenic (score 0.6477) — an in-silico prediction, not a clinical call.

CCR3 p.Phe248Val

c.742T>G · rs148454821 · VCV3140083

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6477 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.124%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6477	likely pathogenic
REVEL	0.607	indeterminate
SaProt	LLR -12.14	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 1,064 bp · p 0.38 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.124% African / African-American · 93/74,872 alleles

Filtering AF 0.104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0962%

Overall 0.00638% 103/1,613,956 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.124%	805
Middle Eastern	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0096%	10,415
Admixed American	0.005%	20,002

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: CCR3
Protein: p.Phe248Val
Coding: c.742T>G
MANE Select: NM_178329
dbSNP: rs148454821
Type: single nucleotide variant
Location: chr3:46265900 (GRCh38)
Gene constraint: LOEUF 1.925 · pLI 0.13 (gnomAD)
Structure: AlphaFold pLDDT 83.72 · 1 PDB
Residue 248: an α-helix

Full CCR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCR3 p.Ala138Ser Uncertain significance ★ ⚠ same type
CCR3 p.Ala216Thr Uncertain significance ★ ⚠ same type
CCR3 p.Ala246Thr Uncertain significance ★ ⚠ same type
CCR3 p.Arg143Gln Uncertain significance ★ ⚠ same type
CCR3 p.Arg202Thr Uncertain significance ★ ⚠ same type
CCR3 p.Arg239Gln Uncertain significance ★ ⚠ same type
CCR3 p.Arg307Ser Uncertain significance ★ ⚠ same type
CCR3 p.Arg309Trp 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/ccr3-p-phe248val (accessed [today's date]).

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