Is VWF p.Val1295Ala (c.3884T>C) pathogenic?

VWF p.Val1295Ala (c.3884T>C) is classified Uncertain significance in VWF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-13). AlphaMissense: likely benign (0.1201); Ultra-rare (popmax 0.0495%, mid); Associated with Inborn genetic diseases.

What condition is associated with VWF p.Val1295Ala (c.3884T>C)?

VWF p.Val1295Ala (c.3884T>C) is associated with Inborn genetic diseases (ClinVar).

How common is VWF p.Val1295Ala (c.3884T>C) in the general population?

VWF p.Val1295Ala (c.3884T>C) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

What do computational predictors say about VWF p.Val1295Ala (c.3884T>C)?

AlphaMissense predicts likely benign (score 0.1201) — an in-silico prediction, not a clinical call.

VWF p.Val1295Ala

c.3884T>C · VCV3468921

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1201 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1201	likely benign
REVEL	0.352	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.31	GERP 0.46
Regional constraint	o/e 0.72	unconstrained · MANE · 30 kb · p 3e-21 · regional, not allelic
Overall
CADD	10.21	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0495% Middle Eastern · 3/6,056 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00719%

Overall 0.000248% 4/1,613,978 alleles · ultra-rare exomes 4/1,461,664 · genomes 0/152,314 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,019
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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.Val1295Ala
Coding: c.3884T>C
MANE Select: NM_000552
Type: single nucleotide variant
Location: chr12:6019534 (GRCh38)
Gene constraint: LOEUF 0.639 · pLI <0.01 (gnomAD)
Residue 1295: the vwfa 1; binding site for platelet glycoprotein ib domain; an α-helix

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-val1295ala (accessed [today's date]).

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