Is ADPGK p.Ser34Phe (c.101C>T) pathogenic?

ADPGK p.Ser34Phe (c.101C>T) is classified Uncertain significance in ADPGK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-26). Very rare (popmax 0.00785%, eas).

How common is ADPGK p.Ser34Phe (c.101C>T) in the general population?

ADPGK p.Ser34Phe (c.101C>T) is very rare (popmax 0.00785%, eas) (gnomAD).

ADPGK p.Ser34Phe

c.101C>T · VCV3273530

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00785%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.081	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.8	GERP 1.5, phastCons 1
Regional constraint	o/e 1.31	unconstrained · MANE · 215 bp · p 0.0013 · regional, not allelic
Overall
CADD	21.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00785% East Asian · 3/38,230 alleles

Filtering AF 0.00208% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00154%

Overall 0.00224% 34/1,516,286 alleles · very rare exomes 32/1,364,040 · genomes 2/152,246 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00785%	12,743
European (non-Finnish)	0.00254%	39,321
Remaining individualsnot grpmax-eligible	0.00169%	59,160
South Asian	0.00122%	81,796

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.Ser34Phe
Coding: c.101C>T
MANE Select: NM_001365225
Type: single nucleotide variant
Location: chr15:72783591 (GRCh38)
Gene constraint: LOEUF 0.937 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.36

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-ser34phe (accessed [today's date]).

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