Is CCR3 p.Ser343Phe (c.1028C>T) pathogenic?

CCR3 p.Ser343Phe (c.1028C>T) is classified Uncertain significance in CCR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-25). AlphaMissense: likely benign (0.1453); Ultra-rare (popmax 0.0758%, eas).

How common is CCR3 p.Ser343Phe (c.1028C>T) in the general population?

CCR3 p.Ser343Phe (c.1028C>T) is ultra-rare (popmax 0.0758%, eas) (gnomAD).

What do computational predictors say about CCR3 p.Ser343Phe (c.1028C>T)?

AlphaMissense predicts likely benign (score 0.1453) — an in-silico prediction, not a clinical call.

CCR3 p.Ser343Phe

c.1028C>T · rs777044791 · VCV2348139

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1453 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0758%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1453	likely benign
REVEL	0.267	benign-leaning
SaProt	LLR -8.80	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 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 1,064 bp · p 0.38 · regional, not allelic
Overall
CADD	23.9	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 0.0758% East Asian · 34/44,872 alleles

Filtering AF 0.0557% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0488%

Overall 0.00239% 35/1,461,540 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0758%	1,320
Remaining individualsnot grpmax-eligible	0.0016%	62,492

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.Ser343Phe
Coding: c.1028C>T
MANE Select: NM_178329
dbSNP: rs777044791
Type: single nucleotide variant
Location: chr3:46266186 (GRCh38)
Gene constraint: LOEUF 1.925 · pLI 0.13 (gnomAD)
Structure: AlphaFold pLDDT 83.72 · 1 PDB

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-ser343phe (accessed [today's date]).

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