Is GP6 p.Thr248= (c.744C>T) pathogenic?

GP6 p.Thr248= (c.744C>T) is classified Likely benign in GP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-24). Very rare (popmax 0.00167%, amr).

How common is GP6 p.Thr248= (c.744C>T) in the general population?

GP6 p.Thr248= (c.744C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

GP6 p.Thr248=

c.744C>T · VCV4699259

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 -0.36	GERP -2.3
Overall
CADD	1.144	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,920 alleles

Filtering AF 0.00019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000125%

Overall 0.000448% 7/1,562,990 alleles · very rare exomes 7/1,410,810 · genomes 0/152,180 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,920
European (non-Finnish)	0.00053%	188,842

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.Thr248=
Coding: c.744C>T
MANE Select: NM_016363
Type: single nucleotide variant
Location: chr19:55015714 (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-thr248 (accessed [today's date]).

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