Is AGL p.Pro503Ser (c.1507C>T) pathogenic?

AGL p.Pro503Ser (c.1507C>T) is classified Uncertain significance in AGL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-18). AlphaMissense: likely benign (0.2327); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with AGL p.Pro503Ser (c.1507C>T)?

AGL p.Pro503Ser (c.1507C>T) is associated with Inborn genetic diseases (ClinVar).

How common is AGL p.Pro503Ser (c.1507C>T) in the general population?

AGL p.Pro503Ser (c.1507C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGL p.Pro503Ser (c.1507C>T)?

AlphaMissense predicts likely benign (score 0.2327) — an in-silico prediction, not a clinical call.

AGL p.Pro503Ser

c.1507C>T · rs2524621311 · VCV2522411

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2327 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2327	likely benign
REVEL	0.726	pathogenic-leaning
SaProt	LLR -10.08	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 71 kb · p 0.78 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AGL
Protein: p.Pro503Ser
Coding: c.1507C>T
MANE Select: NM_000642
dbSNP: rs2524621311
Type: single nucleotide variant
Location: chr1:99877724 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.88 · 1 PDB
Residue 503: the 'amylo-1,6-glucosidase' region; an α-helix

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.Pro503= 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
AGL p.Arg1000Cys Uncertain significance ★★ ⚠ same condition
AGL p.Arg1116His 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-pro503ser (accessed [today's date]).

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