Is GP6 p.Ile281= (c.843A>T) pathogenic?

GP6 p.Ile281= (c.843A>T) is classified Uncertain significance in GP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-07). Ultra-rare (popmax 0.0723%, amr).

How common is GP6 p.Ile281= (c.843A>T) in the general population?

GP6 p.Ile281= (c.843A>T) is ultra-rare (popmax 0.0723%, amr) (gnomAD).

GP6 p.Ile281=

c.843A>T · rs201436629 · VCV2047681

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0723%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.055	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.9	GERP -2.5
Overall
CADD	1.218	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0723% Admixed American · 41/56,710 alleles

Filtering AF 0.0547% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0486%

Overall 0.00545% 87/1,594,992 alleles · ultra-rare exomes 47/1,442,764 · genomes 40/152,228 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0723%	1,383
Middle Eastern	0.0166%	6,036
African / African-American	0.0161%	6,219
Remaining individualsnot grpmax-eligible	0.0146%	6,861
European (non-Finnish)	0.00205%	48,794

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.Ile281=
Coding: c.843A>T
MANE Select: NM_016363
dbSNP: rs201436629
Type: single nucleotide variant
Location: chr19:55015098 (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

Similar variants

GP6 p.Trp160Ter Pathogenic ★★ same type
GP6 c.*106A>C Uncertain significance ★★ same type
GP6 c.*189C>T Uncertain significance ★★ same type
GP6 c.*304C>T Uncertain significance ★★ same type
GP6 c.*523G>C Uncertain significance ★★ same type
GP6 c.*531T>C Uncertain significance ★★ same type
GP6 c.*820T>C Uncertain significance ★★ same type
GP6 p.Arg262Cys Uncertain significance ★★ ⚠ 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/gp6-p-ile281 (accessed [today's date]).

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