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

GMPPA p.Arg272= (c.816G>A) is classified Likely benign in GMPPA (ClinVar, Single submitter, 1 submitter; last evaluated 2016-06-28). Ultra-rare (popmax 0.0497%, mid).

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

GMPPA p.Arg272= (c.816G>A) is ultra-rare (popmax 0.0497%, mid) (gnomAD).

GMPPA p.Arg272=

c.816G>A · rs369505327 · VCV386933

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0497%, mid)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.2	GERP -2.4, phastCons 0.18
Overall
CADD	7.031	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0497% Middle Eastern · 3/6,034 alleles

Filtering AF 0.0135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00721%

Overall 0.00318% 50/1,572,630 alleles · ultra-rare exomes 46/1,420,482 · genomes 4/152,148 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0497%	2,011
Ashkenazi Jewishnot grpmax-eligible	0.0174%	5,753
European (non-Finnish)	0.00345%	28,973
Remaining individualsnot grpmax-eligible	0.00328%	30,510

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: GMPPA
Protein: p.Arg272=
Coding: c.816G>A
MANE Select: NM_013335
dbSNP: rs369505327
Type: single nucleotide variant
Location: chr2:219505518 (GRCh38)

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

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/gmppa-p-arg272 (accessed [today's date]).

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