Is GP6 p.Val238fs (c.711dup) pathogenic?

GP6 p.Val238fs (c.711dup) is classified Pathogenic in GP6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-18). Ultra-rare (popmax 0.0217%, amr); Associated with platelet-type bleeding disorder 11.

What condition is associated with GP6 p.Val238fs (c.711dup)?

GP6 p.Val238fs (c.711dup) is associated with platelet-type bleeding disorder 11 (ClinVar).

How common is GP6 p.Val238fs (c.711dup) in the general population?

GP6 p.Val238fs (c.711dup) is ultra-rare (popmax 0.0217%, amr) (gnomAD).

GP6 p.Val238fs

c.711dup · rs778336022 · VCV1072837

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, amr)

Conditions

platelet-type bleeding disorder 11

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.12	GERP -0.11
Overall
CADD	20.6	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0217% Admixed American · 13/59,990 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.000813% 13/1,599,662 alleles · ultra-rare exomes 12/1,447,438 · genomes 1/152,224 · joint denominator

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: GP6
Protein: p.Val238fs
Coding: c.711dup
MANE Select: NM_016363
dbSNP: rs778336022
Type: Duplication
Location: chr19:55018664 (GRCh38)
Gene constraint: LOEUF 1.734 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 76.52 · 6 PDB

Full GP6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

platelet-type bleeding disorder 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GP6 p.Asn236fs Pathogenic/Likely pathogenic ★★ same condition
GP6 p.Gln119fs Pathogenic/Likely pathogenic ★★ same condition
GP6 c.*395C>T Benign ★★ same condition
GP6 c.*485C>T Likely benign ★★ same condition
GP6 c.*693A>G Benign ★★ same condition
GP6 c.*792T>C Benign ★★ same condition
GP6 p.Ala249Thr Benign ★★ same condition
GP6 p.Arg162= Benign ★★ 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/gp6-p-val238fs (accessed [today's date]).

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