Is VWF p.Val862= (c.2586G>T) pathogenic?

VWF p.Val862= (c.2586G>T) is classified Likely benign in VWF (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-06-02). Rare (popmax 0.709%, mid).

How common is VWF p.Val862= (c.2586G>T) in the general population?

VWF p.Val862= (c.2586G>T) is rare (popmax 0.709%, mid) (gnomAD).

VWF p.Val862=

c.2586G>T · rs34510401 · VCV439329

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.709%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.14	GERP -2.2, phastCons 0.37
Overall
CADD	1.523	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.709% Middle Eastern · 43/6,062 alleles

Filtering AF 0.61% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.592%

Overall 0.132% 2,130/1,614,248 alleles · rare exomes 1,940/1,461,890 · genomes 190/152,358 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.92%	52
Middle Easterngrpmax	0.709%	141
South Asian	0.653%	153
Remaining individualsnot grpmax-eligible	0.243%	411
Admixed American	0.158%	632
Finnishnot grpmax-eligible	0.0625%	1,601
European (non-Finnish)	0.0536%	1,864
African / African-American	0.00533%	18,767

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val862=
Coding: c.2586G>T
MANE Select: NM_000552
dbSNP: rs34510401
Type: single nucleotide variant
Location: chr12:6034787 (GRCh38)
Gene constraint: LOEUF 0.639 · pLI <0.01 (gnomAD)
Residue 862: an α-helix

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

Similar variants

VWF p.Arg1306Trp Pathogenic ★★★ ⚠ same type
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
VWF p.Arg1341Trp Pathogenic ★★★ ⚠ same type
VWF p.Arg1374His 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-val862 (accessed [today's date]).

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