Is WIPF1 p.Pro13= (c.39G>A) pathogenic?

WIPF1 p.Pro13= (c.39G>A) is classified Likely benign in WIPF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-08). Ultra-rare (popmax 0.0185%, amr); Associated with Wiskott-Aldrich syndrome 2.

What condition is associated with WIPF1 p.Pro13= (c.39G>A)?

WIPF1 p.Pro13= (c.39G>A) is associated with Wiskott-Aldrich syndrome 2 (ClinVar).

How common is WIPF1 p.Pro13= (c.39G>A) in the general population?

WIPF1 p.Pro13= (c.39G>A) is ultra-rare (popmax 0.0185%, amr) (gnomAD).

WIPF1 p.Pro13=

c.39G>A · rs143623121 · VCV1545497

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0185%, amr)

Conditions

Wiskott-Aldrich syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.4	GERP -3.5
Overall
CADD	1.516	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0185% Admixed American · 4/21,638 alleles

Filtering AF 0.0063% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00379%

Overall 0.00558% 22/394,276 alleles · ultra-rare exomes 21/326,602 · genomes 1/67,674 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0185%	5,409
Remaining individualsnot grpmax-eligible	0.00739%	13,538
European (non-Finnish)	0.00615%	16,253
South Asian	0.00512%	19,536

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: WIPF1
Protein: p.Pro13=
Coding: c.39G>A
MANE Select: NM_001375834
dbSNP: rs143623121
Type: single nucleotide variant
Location: chr2:174585535 (GRCh38)
Gene constraint: LOEUF 0.565 · pLI 0.83 (gnomAD)
Structure: AlphaFold pLDDT 59.19 · 5 PDB
Residue 13: the 'disordered' region

Full WIPF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Wiskott-Aldrich syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

WIPF1 p.Pro13Leu Uncertain significance ★★ ⚠ same residue
WIPF1 p.Ala259Val Uncertain significance ★★ ⚠ same condition
WIPF1 p.Ala281Pro Uncertain significance ★★ ⚠ same condition
WIPF1 p.Arg125Gln Uncertain significance ★★ ⚠ same condition
WIPF1 p.Arg201Trp Uncertain significance ★★ ⚠ same condition
WIPF1 p.Arg393Trp Uncertain significance ★★ ⚠ same condition
WIPF1 p.Arg485Gln Uncertain significance ★★ ⚠ same condition
WIPF1 p.Arg485Trp 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/wipf1-p-pro13 (accessed [today's date]).

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