Is U2AF2 p.Pro138= (c.414C>T) pathogenic?

U2AF2 p.Pro138= (c.414C>T) is classified Likely benign in U2AF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-24). Ultra-rare (popmax 0.0213%, afr); Associated with Inborn genetic diseases.

What condition is associated with U2AF2 p.Pro138= (c.414C>T)?

U2AF2 p.Pro138= (c.414C>T) is associated with Inborn genetic diseases (ClinVar).

How common is U2AF2 p.Pro138= (c.414C>T) in the general population?

U2AF2 p.Pro138= (c.414C>T) is ultra-rare (popmax 0.0213%, afr) (gnomAD).

U2AF2 p.Pro138=

c.414C>T · VCV3464857

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0213%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -6.4	GERP -3.5
Overall
CADD	4.62	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0213% African / African-American · 16/74,952 alleles

Filtering AF 0.0133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.00267% 43/1,612,762 alleles · ultra-rare exomes 34/1,460,566 · genomes 9/152,196 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0213%	4,684
Admixed American	0.00334%	29,975
Remaining individualsnot grpmax-eligible	0.0032%	31,216
South Asian	0.0022%	45,503
European (non-Finnish)	0.00178%	56,149

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.Pro138=
Coding: c.414C>T
MANE Select: NM_007279
Type: single nucleotide variant
Location: chr19:55661117 (GRCh38)
Gene constraint: LOEUF 0.209 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.24 · 40 PDB

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-pro138 (accessed [today's date]).

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