Is GLUD1 p.Pro16= (c.48C>G) pathogenic?

GLUD1 p.Pro16= (c.48C>G) is classified Likely benign in GLUD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-13). Very rare (popmax 0.00186%, nfe); Associated with hyperinsulinism-hyperammonemia syndrome.

What condition is associated with GLUD1 p.Pro16= (c.48C>G)?

GLUD1 p.Pro16= (c.48C>G) is associated with hyperinsulinism-hyperammonemia syndrome (ClinVar).

How common is GLUD1 p.Pro16= (c.48C>G) in the general population?

GLUD1 p.Pro16= (c.48C>G) is very rare (popmax 0.00186%, nfe) (gnomAD).

How is Hyperinsulinism-hyperammonemia syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

GLUD1 p.Pro16=

c.48C>G · rs1313982001 · VCV1099454

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00186%, nfe)

Conditions

hyperinsulinism-hyperammonemia syndrome

⚠ 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 0.17	GERP -1.7, phastCons 0.85
Overall
CADD	7.465	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00186% European (non-Finnish) · 21/1,130,282 alleles

Filtering AF 0.00119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00101%

Overall 0.00139% 21/1,513,212 alleles · very rare exomes 16/1,361,888 · genomes 5/151,324 · 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: GLUD1
Protein: p.Pro16=
Coding: c.48C>G
MANE Select: NM_005271
dbSNP: rs1313982001
Type: single nucleotide variant
Location: chr10:87094722 (GRCh38)

Full GLUD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hyperinsulinism-hyperammonemia syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hyperinsulinism-hyperammonemia syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal

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/glud1-p-pro16 (accessed [today's date]).

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