Is VWF p.Val490= (c.1470G>C) pathogenic?

VWF p.Val490= (c.1470G>C) is classified Likely benign in VWF (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-04-30). Rare (popmax 0.102%, eas); Associated with Inborn genetic diseases.

What condition is associated with VWF p.Val490= (c.1470G>C)?

VWF p.Val490= (c.1470G>C) is associated with Inborn genetic diseases (ClinVar).

How common is VWF p.Val490= (c.1470G>C) in the general population?

VWF p.Val490= (c.1470G>C) is rare (popmax 0.102%, eas) (gnomAD).

VWF p.Val490=

c.1470G>C · VCV3374928

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.102%, eas)

Conditions

Inborn genetic diseases

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 1.1	GERP 0.36, phastCons 1
Overall
CADD	3.387	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.102% East Asian · 46/44,886 alleles

Filtering AF 0.0789% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0706%

Overall 0.00322% 52/1,613,760 alleles · rare exomes 34/1,461,410 · genomes 18/152,350 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.102%	976
Remaining individualsnot grpmax-eligible	0.008%	12,502
Admixed American	0.00167%	60,030

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: VWF
Protein: p.Val490=
Coding: c.1470G>C
MANE Select: NM_000552
Type: single nucleotide variant
Location: chr12:6063017 (GRCh38)
Gene constraint: LOEUF 0.639 · pLI <0.01 (gnomAD)
Residue 490: a β-strand; the vwfd 2 domain

Full VWF 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

VWF p.Val490Leu Uncertain significance ★ ⚠ same residue
VWF p.Val490Met Uncertain significance ★ same residue
VWF p.Glu383Ter Pathogenic ★★ same condition
VWF p.Ala1207Ser Uncertain significance ★★ ⚠ same condition
VWF p.Ala1420Thr Uncertain significance ★★ same condition
VWF p.Ala2155Ser Uncertain significance ★★ ⚠ same condition
VWF p.Ala465Pro Uncertain significance ★★ same condition
VWF p.Ala54Val 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/vwf-p-val490 (accessed [today's date]).

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