Is AGL p.His412Arg (c.1235A>G) pathogenic?

AGL p.His412Arg (c.1235A>G) is classified Uncertain significance in AGL (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-02-03). AlphaMissense: likely benign (0.1732); Very rare (popmax 0.00333%, amr); Associated with Inborn genetic diseases.

What condition is associated with AGL p.His412Arg (c.1235A>G)?

AGL p.His412Arg (c.1235A>G) is associated with Inborn genetic diseases, glycogen storage disease III (ClinVar).

How common is AGL p.His412Arg (c.1235A>G) in the general population?

AGL p.His412Arg (c.1235A>G) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about AGL p.His412Arg (c.1235A>G)?

AlphaMissense predicts likely benign (score 0.1732) — an in-silico prediction, not a clinical call.

AGL p.His412Arg

c.1235A>G · rs762046235 · VCV1023992

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1732 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1732	likely benign
REVEL	0.403	indeterminate
SaProt	LLR -8.13	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 1.9, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 71 kb · p 0.78 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00333% Admixed American · 2/60,014 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.00031% 5/1,614,050 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,007
African / African-American	0.00267%	37,465
European (non-Finnish)	8.47e-05%	1,180,018

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.His412Arg
Coding: c.1235A>G
MANE Select: NM_000642
dbSNP: rs762046235
Type: single nucleotide variant
Location: chr1:99875407 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.88 · 1 PDB
Residue 412: 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

Also linked: glycogen storage disease III

Similar variants

AGL p.His412Tyr Uncertain significance ★ ⚠ same residue
AGL c.1283+2T>C Likely pathogenic ★★ same condition
AGL c.1284-1G>A Likely pathogenic ★★ same condition
AGL c.1284-2A>G Likely pathogenic ★★ same condition
AGL c.1423+1G>A Pathogenic ★★ same condition
AGL c.1423+1G>C Pathogenic ★★ same condition
AGL c.1423+1G>T Pathogenic/Likely pathogenic ★★ same condition
AGL c.1612-1G>A Pathogenic/Likely pathogenic ★★ 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-his412arg (accessed [today's date]).

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