Is VWF p.Arg1306Pro (c.3917G>C) pathogenic?

VWF p.Arg1306Pro (c.3917G>C) is classified Likely pathogenic in VWF (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-30). AlphaMissense: likely pathogenic (0.6112); Absent from gnomAD v4.1.

How common is VWF p.Arg1306Pro (c.3917G>C) in the general population?

VWF p.Arg1306Pro (c.3917G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about VWF p.Arg1306Pro (c.3917G>C)?

AlphaMissense predicts likely pathogenic (score 0.6112) — an in-silico prediction, not a clinical call.

VWF p.Arg1306Pro

c.3917G>C · rs61749385 · VCV811125

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6112 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.6112	likely pathogenic ✓ concordant with ClinVar
REVEL	0.729	pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.4	GERP 1.6, phastCons 0.77
Regional constraint	o/e 0.72	unconstrained · MANE · 30 kb · p 3e-21 · regional, not allelic
Overall
CADD	23.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: VWF
Protein: p.Arg1306Pro
Coding: c.3917G>C
MANE Select: NM_000552
dbSNP: rs61749385
Type: single nucleotide variant
Location: chr12:6019501 (GRCh38)
Gene constraint: LOEUF 0.639 · pLI <0.01 (gnomAD)
Residue 1306: the vwfa 1; binding site for platelet glycoprotein ib domain; a UniProt-annotated variant site (in vwd2)

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

Similar variants

VWF p.Arg1306Trp Pathogenic ★★★ ⚠ same residue
VWF p.Arg1306Gln Pathogenic ★★ ⚠ same residue
VWF p.Arg1306Leu Pathogenic ★ ⚠ same residue
VWF p.Arg1308Cys Pathogenic ★★★ ⚠ same type
VWF p.Arg1315His Likely pathogenic ★★★ ⚠ same type
VWF p.Arg1315Leu Likely pathogenic ★★★ same type
VWF p.Arg1334Trp Likely pathogenic ★★★ ⚠ same type
VWF p.Arg1341Gln Pathogenic ★★★ ⚠ same type

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-arg1306pro (accessed [today's date]).

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