Is PRKAG3 p.Pro3= (c.9C>T) pathogenic?

PRKAG3 p.Pro3= (c.9C>T) is classified Benign in PRKAG3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Common (popmax 6.9%, afr) — too common for a highly-penetrant pathogenic allele.

PRKAG3 p.Pro3=

Q: How common is PRKAG3 p.Pro3= (c.9C>T) in the general population?

PRKAG3 p.Pro3= (c.9C>T) is common (popmax 6.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.9C>T · rs60578863 · VCV790516

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 6.9%, afr) — too common for a highly-penetrant pathogenic allele

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 -3.9	GERP -3.6
Overall
CADD	0.65	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.9% African / African-American · 5,172/75,002 alleles

Filtering AF 6.74% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.67%

Overall 0.368% 5,920/1,610,330 alleles · common exomes 2,876/1,458,032 · genomes 3,044/152,298 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.9%	15
Admixed American	0.547%	183
Remaining individualsnot grpmax-eligible	0.467%	214
Middle Eastern	0.132%	758
South Asian	0.0145%	6,914
European (non-Finnish)	0.00916%	10,916
East Asian	0.00447%	22,381

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: PRKAG3
Protein: p.Pro3=
Coding: c.9C>T
MANE Select: NM_017431
dbSNP: rs60578863
Type: single nucleotide variant
Location: chr2:218831762 (GRCh38)
Gene constraint: LOEUF 0.895 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.68
Residue 3: the 'disordered' region

Full PRKAG3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRKAG3 p.Phe206= Benign/Likely benign ★★ same type
PRKAG3 p.Pro313= Likely benign ★★ same type
PRKAG3 c.229+1G>T Uncertain significance ★ same type
PRKAG3 p.Ala100Pro Uncertain significance ★ ⚠ same type
PRKAG3 p.Ala102Asp Uncertain significance ★ ⚠ same type
PRKAG3 p.Ala123Thr Uncertain significance ★ ⚠ same type
PRKAG3 p.Ala158Pro Uncertain significance ★ ⚠ same type
PRKAG3 p.Ala181Pro 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/prkag3-p-pro3 (accessed [today's date]).

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