Is GP6 p.Ala20= (c.60G>A) pathogenic?

GP6 p.Ala20= (c.60G>A) is classified Likely benign in GP6 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-25). Ultra-rare (popmax 0.0373%, afr).

How common is GP6 p.Ala20= (c.60G>A) in the general population?

GP6 p.Ala20= (c.60G>A) is ultra-rare (popmax 0.0373%, afr) (gnomAD).

GP6 p.Ala20=

c.60G>A · rs201025246 · VCV2200595

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0373%, 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 -4.2	GERP -3.7
Overall
CADD	3.328	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0373% African / African-American · 28/75,064 alleles

Filtering AF 0.0265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0229%

Overall 0.0142% 229/1,613,834 alleles · ultra-rare exomes 207/1,461,492 · genomes 22/152,342 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0373%	2,681
Middle Eastern	0.0165%	6,044
European (non-Finnish)	0.0154%	6,483
Remaining individualsnot grpmax-eligible	0.0128%	7,812
Ashkenazi Jewishnot grpmax-eligible	0.00675%	14,804
East Asian	0.00668%	14,961
South Asian	0.00549%	18,212

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.Ala20=
Coding: c.60G>A
MANE Select: NM_016363
dbSNP: rs201025246
Type: single nucleotide variant
Location: chr19:55032513 (GRCh38)
Gene constraint: LOEUF 1.734 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 76.52 · 6 PDB

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

Similar variants

GP6 p.Ala20Val Uncertain significance ★ ⚠ same residue
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

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-ala20 (accessed [today's date]).

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