Is WIPF1 p.Pro10= (c.30G>C) pathogenic?

WIPF1 p.Pro10= (c.30G>C) is classified Likely benign in WIPF1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-27). Common (popmax 5.35%, sas) — too common for a highly-penetrant pathogenic allele; Associated with Wiskott-Aldrich syndrome 2.

What condition is associated with WIPF1 p.Pro10= (c.30G>C)?

WIPF1 p.Pro10= (c.30G>C) is associated with Wiskott-Aldrich syndrome 2 (ClinVar).

WIPF1 p.Pro10=

Q: How common is WIPF1 p.Pro10= (c.30G>C) in the general population?

WIPF1 p.Pro10= (c.30G>C) is common (popmax 5.35%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.30G>C · rs745425874 · VCV1109512

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.35%, sas) — too common for a highly-penetrant pathogenic allele

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 -8.4	GERP -3.5
Overall
CADD	0.801	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.35% South Asian · 1,526/28,514 alleles

Filtering AF 5.13% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.04%

Overall 2.2% 6,659/302,142 alleles · common exomes 6,513/260,162 · genomes 146/41,980 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	5.35%	19
Remaining individualsnot grpmax-eligible	2.96%	34
Admixed American	2.33%	43
European (non-Finnish)	2.03%	49
Ashkenazi Jewishnot grpmax-eligible	1.64%	61
Finnishnot grpmax-eligible	1.28%	78
Middle Eastern	1.08%	93
East Asian	1.05%	95
African / African-American	0.666%	150

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.Pro10=
Coding: c.30G>C
MANE Select: NM_001375834
dbSNP: rs745425874
Type: single nucleotide variant
Location: chr2:174585544 (GRCh38)
Gene constraint: LOEUF 0.565 · pLI 0.83 (gnomAD)
Structure: AlphaFold pLDDT 59.19 · 5 PDB
Residue 10: 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.Pro10Leu 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-pro10 (accessed [today's date]).

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