Is U2AF2 p.Ser32Pro (c.94T>C) pathogenic?

U2AF2 p.Ser32Pro (c.94T>C) is classified Uncertain significance in U2AF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-06). AlphaMissense: ambiguous (0.3942); Very rare (popmax 0.00169%, amr); Associated with Inborn genetic diseases.

What condition is associated with U2AF2 p.Ser32Pro (c.94T>C)?

U2AF2 p.Ser32Pro (c.94T>C) is associated with Inborn genetic diseases (ClinVar).

How common is U2AF2 p.Ser32Pro (c.94T>C) in the general population?

U2AF2 p.Ser32Pro (c.94T>C) is very rare (popmax 0.00169%, amr) (gnomAD).

What do computational predictors say about U2AF2 p.Ser32Pro (c.94T>C)?

AlphaMissense predicts ambiguous (score 0.3942) — an in-silico prediction, not a clinical call.

U2AF2 p.Ser32Pro

c.94T>C · VCV3464856

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3942 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00169%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3942	ambiguous
REVEL	0.058	moderately benign-leaning
SaProt	LLR -11.31	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 5,440 bp · p 0.00024 · regional, not allelic
Overall
CADD	26.8	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 0.00169% Admixed American · 1/59,252 alleles

Overall 6.24e-05% 1/1,602,460 alleles · very rare exomes 0/1,450,362 · genomes 1/152,098 · 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: U2AF2
Protein: p.Ser32Pro
Coding: c.94T>C
MANE Select: NM_007279
Type: single nucleotide variant
Location: chr19:55659254 (GRCh38)
Gene constraint: LOEUF 0.209 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.24 · 40 PDB
Residue 32: the 'disordered' region; the 'required for interaction with prpf19' region; the 'necessary and sufficient to stimulate pre-mrnas 3'-end cleavage in a cfim complex-dependent manner' region

Full U2AF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

U2AF2 p.Arg149Trp Pathogenic ★★ same condition
U2AF2 p.His470Gln Uncertain significance ★★ ⚠ same condition
U2AF2 p.Arg37His Uncertain significance ★ ⚠ same condition
U2AF2 p.Arg40Gln Uncertain significance ★ ⚠ same condition
U2AF2 p.Arg40Trp Uncertain significance ★ ⚠ same condition
U2AF2 p.Arg47His Uncertain significance ★ ⚠ same condition
U2AF2 p.Arg49Gln Uncertain significance ★ ⚠ same condition
U2AF2 p.Arg61His Uncertain significance ★ ⚠ same condition

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/u2af2-p-ser32pro (accessed [today's date]).

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