Is GP6 p.Thr6= (c.18C>T) pathogenic?

GP6 p.Thr6= (c.18C>T) is classified Likely benign in GP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-06). Ultra-rare (popmax 0.0347%, afr).

How common is GP6 p.Thr6= (c.18C>T) in the general population?

GP6 p.Thr6= (c.18C>T) is ultra-rare (popmax 0.0347%, afr) (gnomAD).

GP6 p.Thr6=

c.18C>T · rs199807828 · VCV2069259

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0347%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.5	GERP -3.9
Overall
CADD	0.259	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0347% African / African-American · 26/74,874 alleles

Filtering AF 0.0243% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0208%

Overall 0.00478% 76/1,591,612 alleles · ultra-rare exomes 51/1,439,366 · genomes 25/152,246 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0347%	2,880
Remaining individualsnot grpmax-eligible	0.00649%	15,417
European (non-Finnish)	0.00368%	27,161
Admixed American	0.00352%	28,384
South Asian	0.00114%	87,588

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.Thr6=
Coding: c.18C>T
MANE Select: NM_016363
dbSNP: rs199807828
Type: single nucleotide variant
Location: chr19:55038219 (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-thr6 (accessed [today's date]).

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