Is GP6 p.Pro316= (c.948G>A) pathogenic?

GP6 p.Pro316= (c.948G>A) is classified Uncertain significance in GP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-28). Very rare (popmax 0.00332%, nfe); Associated with Inborn genetic diseases.

What condition is associated with GP6 p.Pro316= (c.948G>A)?

GP6 p.Pro316= (c.948G>A) is associated with Inborn genetic diseases (ClinVar).

How common is GP6 p.Pro316= (c.948G>A) in the general population?

GP6 p.Pro316= (c.948G>A) is very rare (popmax 0.00332%, nfe) (gnomAD).

GP6 p.Pro316=

c.948G>A · rs770868762 · VCV2603212

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00332%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.04	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.075	GERP -2, phastCons 0.004
Overall
CADD	5.688	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00332% European (non-Finnish) · 37/1,115,390 alleles

Filtering AF 0.00245% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00214%

Overall 0.00256% 39/1,521,908 alleles · very rare exomes 36/1,374,048 · genomes 3/147,860 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00332%	30,146
African / African-American	0.00291%	34,349

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.Pro316=
Coding: c.948G>A
MANE Select: NM_016363
dbSNP: rs770868762
Type: single nucleotide variant
Location: chr19:55014993 (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 316: 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 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
GP6 p.Arg319Trp 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-pro316 (accessed [today's date]).

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