Is GP6 p.Pro219Ser (c.655C>T) pathogenic?

GP6 p.Pro219Ser (c.655C>T) is classified Benign in GP6 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0629); Common (popmax 98%, eas) — too common for a highly-penetrant pathogenic allele; Associated with platelet-type bleeding disorder 11.

What condition is associated with GP6 p.Pro219Ser (c.655C>T)?

GP6 p.Pro219Ser (c.655C>T) is associated with platelet-type bleeding disorder 11 (ClinVar).

What do computational predictors say about GP6 p.Pro219Ser (c.655C>T)?

AlphaMissense predicts likely benign (score 0.0629) — an in-silico prediction, not a clinical call.

GP6 p.Pro219Ser

Q: How common is GP6 p.Pro219Ser (c.655C>T) in the general population?

GP6 p.Pro219Ser (c.655C>T) is common (popmax 98%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.655C>T · rs1613662 · VCV257422

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0629 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 98%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

platelet-type bleeding disorder 11

Computational evidence

Protein change
AlphaMissense	0.0629	likely benign
REVEL	0.008	strongly benign-leaning
SaProt	LLR -5.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.04	GERP -1.4
Overall
CADD	0.385	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 98% East Asian · 40,101/40,912 alleles

Filtering AF 97.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 96.9%

Overall 84% 1,294,244/1,541,374 alleles · common exomes 1,167,289/1,389,204 · genomes 126,955/152,170 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	98%	1
Admixed American	90.9%	1
Finnishnot grpmax-eligible	88.5%	1
Remaining individualsnot grpmax-eligible	84%	1
European (non-Finnish)	83.9%	1
Middle Eastern	80.5%	1
Ashkenazi Jewishnot grpmax-eligible	79.4%	1
South Asian	79%	1
Amishnot grpmax-eligible	77%	1
African / African-American	77%	1

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.Pro219Ser
Coding: c.655C>T
MANE Select: NM_016363
dbSNP: rs1613662
Type: single nucleotide variant
Location: chr19:55025227 (GRCh38)
Gene constraint: LOEUF 1.734 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 76.52 · 6 PDB
Residue 219: a UniProt-annotated variant site (in)

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.Pro219Leu Uncertain significance ★ ⚠ same residue
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
GP6 p.Glu237Lys 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-pro219ser (accessed [today's date]).

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