Is GP6 p.Val130= (c.390A>T) pathogenic?

GP6 p.Val130= (c.390A>T) is classified Benign/Likely benign in GP6 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-21). Rare (popmax 0.914%, afr).

How common is GP6 p.Val130= (c.390A>T) in the general population?

GP6 p.Val130= (c.390A>T) is rare (popmax 0.914%, afr) (gnomAD).

GP6 p.Val130=

c.390A>T · rs115934645 · VCV2054011

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.914%, afr)

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 0.01	GERP -2.2, phastCons 0.53
Overall
CADD	8.408	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.914% African / African-American · 686/75,068 alleles

Filtering AF 0.857% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.835%

Overall 0.0468% 755/1,614,042 alleles · rare exomes 368/1,461,688 · genomes 387/152,354 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.914%	109
Remaining individualsnot grpmax-eligible	0.0528%	1,894
Admixed American	0.0433%	2,309
Middle Eastern	0.033%	3,031
South Asian	0.00329%	30,363
European (non-Finnish)	0.000424%	235,975

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.Val130=
Coding: c.390A>T
MANE Select: NM_016363
dbSNP: rs115934645
Type: single nucleotide variant
Location: chr19:55027798 (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 130: a β-strand; the ig-like c2-type 2 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-val130 (accessed [today's date]).

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