Is GP6 p.Pro308= (c.924G>A) pathogenic?

GP6 p.Pro308= (c.924G>A) is classified Conflicting classifications of pathogenicity in GP6 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-01-22). Very rare (popmax 0.00893%, eas); Associated with Inborn genetic diseases.

What condition is associated with GP6 p.Pro308= (c.924G>A)?

GP6 p.Pro308= (c.924G>A) is associated with Inborn genetic diseases (ClinVar).

How common is GP6 p.Pro308= (c.924G>A) in the general population?

GP6 p.Pro308= (c.924G>A) is very rare (popmax 0.00893%, eas) (gnomAD).

GP6 p.Pro308=

c.924G>A · rs373346261 · VCV2765638

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00893%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.109	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.5	GERP -1.9
Overall
CADD	6.673	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00893% East Asian · 4/44,798 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00168% 27/1,611,766 alleles · very rare exomes 26/1,459,574 · genomes 1/152,192 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0209%	4,795
East Asiangrpmax	0.00893%	11,200
South Asian	0.00551%	18,147
Admixed American	0.00167%	59,762
African / African-American	0.00134%	74,870
European (non-Finnish)	0.000254%	393,069

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.Pro308=
Coding: c.924G>A
MANE Select: NM_016363
dbSNP: rs373346261
Type: single nucleotide variant
Location: chr19:55015017 (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 308: the 'disordered' region

Full GP6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GP6 p.Pro308Leu Likely benign ★★ same residue
GP6 c.*106A>C Uncertain significance ★★ same condition
GP6 c.*189C>T Uncertain significance ★★ same condition
GP6 c.*304C>T Uncertain significance ★★ same condition
GP6 c.*523G>C Uncertain significance ★★ same condition
GP6 c.*531T>C Uncertain significance ★★ same condition
GP6 p.Arg262Cys Uncertain significance ★★ ⚠ same condition
GP6 p.Arg299Trp Uncertain significance ★★ ⚠ 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-pro308 (accessed [today's date]).

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