Is VWA2 p.Asn331= (c.993C>T) pathogenic?

VWA2 p.Asn331= (c.993C>T) is classified Benign in VWA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-12-20). Common (popmax 7.94%, afr) — too common for a highly-penetrant pathogenic allele.

VWA2 p.Asn331=

Q: How common is VWA2 p.Asn331= (c.993C>T) in the general population?

VWA2 p.Asn331= (c.993C>T) is common (popmax 7.94%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.993C>T · rs11817946 · VCV769372

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 7.94%, 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 looked up on this page · why
Constraint at this position
Conservation	phyloP 3.3	GERP 1.7, phastCons 1
Overall
CADD	9.51	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.94% African / African-American · 5,874/73,974 alleles

Filtering AF 7.77% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.7%

Overall 0.436% 6,958/1,596,234 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.94%	13
Admixed American	0.688%	145
Remaining individualsnot grpmax-eligible	0.599%	167
Middle Eastern	0.371%	269
European (non-Finnish)	0.0239%	4,188
South Asian	0.0205%	4,886

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: VWA2
Protein: p.Asn331=
Coding: c.993C>T
MANE Select: NM_001001936 · reported on NM_001272046
dbSNP: rs11817946
Type: single nucleotide variant
Location: chr10:114284966 (GRCh38)

Full VWA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/vwa2-p-asn331 (accessed [today's date]).

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