Is VWF p.Ser2479Pro (c.7435T>C) pathogenic?

VWF p.Ser2479Pro (c.7435T>C) is classified Likely benign in VWF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: likely benign (0.0511); Very rare (popmax 0.000254%, nfe); Associated with Inborn genetic diseases.

What condition is associated with VWF p.Ser2479Pro (c.7435T>C)?

VWF p.Ser2479Pro (c.7435T>C) is associated with Inborn genetic diseases (ClinVar).

How common is VWF p.Ser2479Pro (c.7435T>C) in the general population?

VWF p.Ser2479Pro (c.7435T>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about VWF p.Ser2479Pro (c.7435T>C)?

AlphaMissense predicts likely benign (score 0.0511) — an in-silico prediction, not a clinical call.

VWF p.Ser2479Pro

c.7435T>C · VCV4634576

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0511 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0511	likely benign
REVEL	0.113	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.067	GERP -3.2
Regional constraint	o/e 0.89	unconstrained · MANE · 47 kb · p 0.00012 · regional, not allelic
Overall
CADD	2.214	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,014 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,536 alleles · very rare

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.Ser2479Pro
Coding: c.7435T>C
MANE Select: NM_000552
Type: single nucleotide variant
Location: chr12:5976113 (GRCh38)
Gene constraint: LOEUF 0.639 · pLI <0.01 (gnomAD)
Residue 2479: the vwfc 2 domain; a disulfide bond

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.Ser2479Leu Uncertain significance ★ ⚠ same residue
VWF p.Ser2479= Pathogenic 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-ser2479pro (accessed [today's date]).

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