Is GP6 p.Pro197Arg (c.590C>G) pathogenic?

GP6 p.Pro197Arg (c.590C>G) is classified Uncertain significance in GP6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-10). AlphaMissense: likely benign (0.2312); Very rare (popmax 0.00483%, nfe); Associated with Inborn genetic diseases.

What condition is associated with GP6 p.Pro197Arg (c.590C>G)?

GP6 p.Pro197Arg (c.590C>G) is associated with Inborn genetic diseases (ClinVar).

How common is GP6 p.Pro197Arg (c.590C>G) in the general population?

GP6 p.Pro197Arg (c.590C>G) is very rare (popmax 0.00483%, nfe) (gnomAD).

What do computational predictors say about GP6 p.Pro197Arg (c.590C>G)?

AlphaMissense predicts likely benign (score 0.2312) — an in-silico prediction, not a clinical call.

GP6 p.Pro197Arg

c.590C>G · rs778314910 · VCV2068613

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2312 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00483%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2312	likely benign
REVEL	0.166	moderately benign-leaning
SaProt	LLR -11.46	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.6	GERP 2.2, phastCons 0.99
Overall
CADD	23.9	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 0.00483% European (non-Finnish) · 57/1,179,436 alleles

Filtering AF 0.00378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00345%

Overall 0.00384% 62/1,613,276 alleles · very rare exomes 58/1,461,048 · genomes 4/152,228 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00483%	20,692
Admixed American	0.00333%	30,004
Remaining individualsnot grpmax-eligible	0.0032%	31,234
African / African-American	0.00133%	74,936

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.Pro197Arg
Coding: c.590C>G
MANE Select: NM_016363
dbSNP: rs778314910
Type: single nucleotide variant
Location: chr19:55027598 (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 197: an α-helix

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.Pro197Leu Uncertain significance ★ ⚠ 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-pro197arg (accessed [today's date]).

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