Is WSB2 p.Asp4= (c.12C>T) pathogenic?

WSB2 p.Asp4= (c.12C>T) is classified Benign in WSB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-04). Common (popmax 14.2%, afr) — too common for a highly-penetrant pathogenic allele.

WSB2 p.Asp4=

Q: How common is WSB2 p.Asp4= (c.12C>T) in the general population?

WSB2 p.Asp4= (c.12C>T) is common (popmax 14.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.12C>T · rs77531942 · VCV768591

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 14.2%, afr) — too common for a highly-penetrant pathogenic allele

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 -1.3	GERP -0.73
Overall
CADD	3.955	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 14.2% African / African-American · 10,402/73,002 alleles

Filtering AF 14% ClinGen BA1/BS1 input FAF95, joint · FAF99 13.9%

Overall 0.801% 12,305/1,535,334 alleles · common exomes 6,129/1,383,246 · genomes 6,176/152,088 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	14.2%	7
Admixed American	1.19%	84
Remaining individualsnot grpmax-eligible	1.12%	89
Middle Eastern	0.952%	105
Ashkenazi Jewishnot grpmax-eligible	0.318%	315
South Asian	0.044%	2,272
European (non-Finnish)	0.038%	2,630
East Asian	0.00245%	40,888

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: WSB2
Protein: p.Asp4=
Coding: c.12C>T
MANE Select: NM_018639 · reported on NM_001278557
dbSNP: rs77531942
Type: single nucleotide variant
Location: chr12:118062151 (GRCh38)
Gene constraint: LOEUF 0.363 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.84

Full WSB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

WSB2 p.Thr162Ala Benign ★★ same type
WSB2 c.14-5C>G Uncertain significance ★ same type
WSB2 p.Arg113His Uncertain significance ★ ⚠ same type
WSB2 p.Arg80Trp Uncertain significance ★ ⚠ same type
WSB2 p.Gly79Glu Uncertain significance ★ ⚠ same type
WSB2 p.Gly96Ala Uncertain significance ★ ⚠ same type
WSB2 p.Ile180Val Uncertain significance ★ ⚠ same type
WSB2 p.Leu88Val 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/wsb2-p-asp4 (accessed [today's date]).

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