Is GP6 p.Arg272= (c.816G>A) pathogenic?

GP6 p.Arg272= (c.816G>A) is classified Uncertain significance in GP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-14). Ultra-rare (popmax 0.0166%, mid); Associated with Inborn genetic diseases.

What condition is associated with GP6 p.Arg272= (c.816G>A)?

GP6 p.Arg272= (c.816G>A) is associated with Inborn genetic diseases (ClinVar).

How common is GP6 p.Arg272= (c.816G>A) in the general population?

GP6 p.Arg272= (c.816G>A) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

GP6 p.Arg272=

c.816G>A · rs772083213 · VCV2350049

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.087	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.011	GERP -1, phastCons 0.038
Overall
CADD	2.779	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0166% Middle Eastern · 1/6,014 alleles

Filtering AF 0.00349% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0024%

Overall 0.00076% 12/1,579,624 alleles · ultra-rare exomes 12/1,427,380 · genomes 0/152,244 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,014
African / African-American	0.00806%	12,400
Remaining individualsnot grpmax-eligible	0.00654%	15,297
European (non-Finnish)	8.6e-05%	1,162,542

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.Arg272=
Coding: c.816G>A
MANE Select: NM_016363
dbSNP: rs772083213
Type: single nucleotide variant
Location: chr19:55015125 (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

Disease context

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

Similar variants

GP6 p.Arg272Gln 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-arg272 (accessed [today's date]).

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