Is AGL p.Val348Ile (c.1042G>A) pathogenic?

AGL p.Val348Ile (c.1042G>A) is classified Uncertain significance in AGL (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-11-03). AlphaMissense: likely benign (0.0909); Ultra-rare (popmax 0.0332%, mid); Associated with Inborn genetic diseases.

What condition is associated with AGL p.Val348Ile (c.1042G>A)?

AGL p.Val348Ile (c.1042G>A) is associated with Inborn genetic diseases, glycogen storage disease III (ClinVar).

How common is AGL p.Val348Ile (c.1042G>A) in the general population?

AGL p.Val348Ile (c.1042G>A) is ultra-rare (popmax 0.0332%, mid) (gnomAD).

What do computational predictors say about AGL p.Val348Ile (c.1042G>A)?

AlphaMissense predicts likely benign (score 0.0909) — an in-silico prediction, not a clinical call.

AGL p.Val348Ile

c.1042G>A · rs544658310 · VCV843349

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0909 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0332%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0909	likely benign
REVEL	0.203	benign-leaning
SaProt	LLR -6.55	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP 0.47, phastCons 0.99
Regional constraint	o/e 0.99	unconstrained · MANE · 71 kb · p 0.78 · regional, not allelic
Overall
CADD	17.23	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 0.0332% Middle Eastern · 2/6,024 alleles

Filtering AF 0.00585% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00429% 69/1,607,732 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0332%	3,012
Remaining individualsnot grpmax-eligible	0.00644%	15,536
European (non-Finnish)	0.00527%	18,975
Admixed American	0.00168%	59,648

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.Val348Ile
Coding: c.1042G>A
MANE Select: NM_000642
dbSNP: rs544658310
Type: single nucleotide variant
Location: chr1:99874770 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.88 · 1 PDB
Residue 348: the 'amylo-1,6-glucosidase' region

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.Val348= Likely benign ★ same residue
AGL p.Val348fs Pathogenic/Likely pathogenic ★★ 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

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-val348ile (accessed [today's date]).

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