Is ADPGK p.Pro53Arg (c.158C>G) pathogenic?

ADPGK p.Pro53Arg (c.158C>G) is classified Uncertain significance in ADPGK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-30). Very rare (popmax 0.00846%, eas).

How common is ADPGK p.Pro53Arg (c.158C>G) in the general population?

ADPGK p.Pro53Arg (c.158C>G) is very rare (popmax 0.00846%, eas) (gnomAD).

ADPGK p.Pro53Arg

c.158C>G · VCV4019621

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00846%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.076	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.8	GERP 1.5, phastCons 1
Regional constraint	o/e 1.31	unconstrained · MANE · 215 bp · p 0.0013 · regional, not allelic
Overall
CADD	21.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00846% East Asian · 3/35,476 alleles

Filtering AF 0.00224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00122%

Overall 0.000201% 3/1,490,084 alleles · very rare exomes 3/1,337,726 · genomes 0/152,358 · joint denominator

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: ADPGK
Protein: p.Pro53Arg
Coding: c.158C>G
MANE Select: NM_001365225
Type: single nucleotide variant
Location: chr15:72783534 (GRCh38)
Gene constraint: LOEUF 0.937 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.36
Residue 53: the adpk domain

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

Similar variants

ADPGK p.Ala146Val Uncertain significance ★ same type
ADPGK p.Ala2Val Uncertain significance ★ same type
ADPGK p.Ala318Thr Uncertain significance ★ same type
ADPGK p.Ala318Val Uncertain significance ★ same type
ADPGK p.Ala416Thr Uncertain significance ★ same type
ADPGK p.Ala429Val Uncertain significance ★ same type
ADPGK p.Ala58Val Uncertain significance ★ same type
ADPGK p.Ala59Val 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/adpgk-p-pro53arg (accessed [today's date]).

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