Is CXCL3 p.Ala32Val (c.95C>T) pathogenic?

CXCL3 p.Ala32Val (c.95C>T) is classified Uncertain significance in CXCL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-15). AlphaMissense: likely benign (0.1276); Very rare (popmax 0.00249%, amr).

How common is CXCL3 p.Ala32Val (c.95C>T) in the general population?

CXCL3 p.Ala32Val (c.95C>T) is very rare (popmax 0.00249%, amr) (gnomAD).

What do computational predictors say about CXCL3 p.Ala32Val (c.95C>T)?

AlphaMissense predicts likely benign (score 0.1276) — an in-silico prediction, not a clinical call.

CXCL3 p.Ala32Val

c.95C>T · rs1374231659 · VCV2458272

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1276 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00249%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1276	likely benign
REVEL	0.123	moderately benign-leaning
SaProt	LLR -7.90	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 1.7	GERP 0.072, phastCons 0.007
Regional constraint	o/e 1.07	unconstrained · MANE · 1,346 bp · p 0.4 · regional, not allelic
Overall
CADD	16.25	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 0.00249% Admixed American · 1/40,160 alleles

Overall 0.000225% 3/1,335,704 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00249%	40,160
Remaining individualsnot grpmax-eligible	0.00175%	57,200
European (non-Finnish)	8.91e-05%	1,122,018

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: CXCL3
Protein: p.Ala32Val
Coding: c.95C>T
MANE Select: NM_002090
dbSNP: rs1374231659
Type: single nucleotide variant
Location: chr4:74038517 (GRCh38)
Gene constraint: LOEUF 1.383 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.50 · 2 PDB

Full CXCL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CXCL3 p.Ala32Ser Uncertain significance ★ ⚠ same residue
CXCL3 p.Ala2Gly Uncertain significance ★ ⚠ same type
CXCL3 p.Ala4Gly Uncertain significance ★ ⚠ same type
CXCL3 p.Ala84Ser Uncertain significance ★ ⚠ same type
CXCL3 p.Ala8Ser Uncertain significance ★ ⚠ same type
CXCL3 p.Arg17Leu Uncertain significance ★ ⚠ same type
CXCL3 p.Arg42Gly Uncertain significance ★ ⚠ same type
CXCL3 p.Arg42His 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/cxcl3-p-ala32val (accessed [today's date]).

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