Is GP6 p.Pro34= (c.102C>T) pathogenic?

GP6 p.Pro34= (c.102C>T) is classified Likely benign in GP6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-03). Very rare (popmax 0.00223%, eas).

How common is GP6 p.Pro34= (c.102C>T) in the general population?

GP6 p.Pro34= (c.102C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

GP6 p.Pro34=

c.102C>T · rs745762025 · VCV2741100

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 -1.2	GERP -4.3
Overall
CADD	8.835	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,880 alleles

Filtering AF 0.00153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00186% 30/1,613,672 alleles · very rare exomes 28/1,461,434 · genomes 2/152,238 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,821
East Asiangrpmax	0.00223%	44,880
European (non-Finnish)	0.0022%	45,379

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro34=
Coding: c.102C>T
MANE Select: NM_016363
dbSNP: rs745762025
Type: single nucleotide variant
Location: chr19:55032362 (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 34: a β-strand; the ig-like c2-type 1 domain

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-pro34 (accessed [today's date]).

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