Is AGL p.Arg34Pro (c.101G>C) pathogenic?

AGL p.Arg34Pro (c.101G>C) is classified Uncertain significance in AGL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-15). AlphaMissense: likely pathogenic (0.9911); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with AGL p.Arg34Pro (c.101G>C)?

AGL p.Arg34Pro (c.101G>C) is associated with Inborn genetic diseases (ClinVar).

How common is AGL p.Arg34Pro (c.101G>C) in the general population?

AGL p.Arg34Pro (c.101G>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about AGL p.Arg34Pro (c.101G>C)?

AlphaMissense predicts likely pathogenic (score 0.9911) — an in-silico prediction, not a clinical call.

AGL p.Arg34Pro

c.101G>C · VCV3276009

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9911 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9911	likely pathogenic · top 3% in AGL
REVEL	0.484	indeterminate
SaProt	LLR -14.21	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.4, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 71 kb · p 0.78 · regional, not allelic
Overall
CADD	27.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,830 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000186% 3/1,613,840 alleles · very rare exomes 3/1,461,622 · genomes 0/152,218 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,830
South Asian	0.0022%	45,528

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: AGL
Protein: p.Arg34Pro
Coding: c.101G>C
MANE Select: NM_000642
Type: single nucleotide variant
Location: chr1:99861521 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.88 · 1 PDB
Residue 34: the 'amylo-1,6-glucosidase' region; a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AGL p.Arg34Ter Pathogenic/Likely pathogenic ★★ same residue
AGL p.Arg34Gln Uncertain significance ★ ⚠ same residue
AGL p.Arg34= Likely benign ★ same residue
AGL c.2681+1G>T Pathogenic/Likely pathogenic ★★ same condition
AGL p.Ala1128Thr Uncertain significance ★★ ⚠ same condition
AGL p.Ala1319Gly Uncertain significance ★★ ⚠ same condition
AGL p.Ala1404Thr Uncertain significance ★★ ⚠ same condition
AGL p.Ala396Val Uncertain significance ★★ ⚠ same condition

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/agl-p-arg34pro (accessed [today's date]).

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