Is VWF p.Ser353= (c.1059C>T) pathogenic?

VWF p.Ser353= (c.1059C>T) is classified Likely benign in VWF (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-10). Ultra-rare (popmax 0.0143%, sas); Associated with Inborn genetic diseases.

What condition is associated with VWF p.Ser353= (c.1059C>T)?

VWF p.Ser353= (c.1059C>T) is associated with Inborn genetic diseases (ClinVar).

How common is VWF p.Ser353= (c.1059C>T) in the general population?

VWF p.Ser353= (c.1059C>T) is ultra-rare (popmax 0.0143%, sas) (gnomAD).

VWF p.Ser353=

c.1059C>T · rs767726061 · VCV2642609

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0143%, sas)

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 -7.8
Overall
CADD	0.066	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0143% South Asian · 13/91,074 alleles

Filtering AF 0.00844% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00661%

Overall 0.00378% 61/1,613,950 alleles · ultra-rare exomes 60/1,461,860 · genomes 1/152,090 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0143%	7,006
East Asian	0.0111%	8,976
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,869
Admixed American	0.00833%	11,999
Remaining individualsnot grpmax-eligible	0.008%	12,497
African / African-American	0.00267%	37,443
European (non-Finnish)	0.00237%	42,144

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.Ser353=
Coding: c.1059C>T
MANE Select: NM_000552
dbSNP: rs767726061
Type: single nucleotide variant
Location: chr12:6072381 (GRCh38)
Gene constraint: LOEUF 0.639 · pLI <0.01 (gnomAD)
Residue 353: a β-strand

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.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
VWF p.Arg1342His Uncertain significance ★★ ⚠ same condition
VWF p.Arg1392Gln 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-ser353 (accessed [today's date]).

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