Is GAA p.Ala486Ser (c.1456G>T) pathogenic?

GAA p.Ala486Ser (c.1456G>T) is classified Conflicting classifications of pathogenicity in GAA (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-07-01). AlphaMissense: likely benign (0.1681); Absent from gnomAD v4.1; Associated with glycogen storage disease II.

What condition is associated with GAA p.Ala486Ser (c.1456G>T)?

GAA p.Ala486Ser (c.1456G>T) is associated with glycogen storage disease II (ClinVar).

How common is GAA p.Ala486Ser (c.1456G>T) in the general population?

GAA p.Ala486Ser (c.1456G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GAA p.Ala486Ser (c.1456G>T)?

AlphaMissense predicts likely benign (score 0.1681) — an in-silico prediction, not a clinical call.

GAA p.Ala486Ser

Q: How is Glycogen storage disease due to acid maltase deficiency inherited?

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

c.1456G>T · rs1283045273 · VCV2752316

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1681 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

glycogen storage disease II

Computational evidence

Protein change
AlphaMissense	0.1681	likely benign
REVEL	0.454	indeterminate
SaProt	LLR -7.98	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 8.4	GERP 1.6, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 15 kb · p 0.22 · regional, not allelic
Overall
CADD	25.0	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: GAA
Protein: p.Ala486Ser
Coding: c.1456G>T
MANE Select: NM_000152
dbSNP: rs1283045273
Type: single nucleotide variant
Location: chr17:80110745 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.32 · 19 PDB
Residue 486: a UniProt-annotated variant site (in lopd); a β-strand

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

Disease context

glycogen storage disease II — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Glycogen storage disease due to acid maltase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

GAA p.Ala486Pro Likely pathogenic ★★★ ⚠ same residue
GAA p.Ala486Val Uncertain significance ★★ ⚠ same residue
GAA p.Ala486= Likely benign ★★ same residue
GAA p.Ala486Thr Uncertain significance ★ ⚠ same residue
GAA p.Ala486fs Pathogenic ★ same residue
GAA c.1076-1G>C Pathogenic ★★★ same condition
GAA c.1076-22T>G Pathogenic ★★★ same condition
GAA c.1194+5G>A 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/gaa-p-ala486ser (accessed [today's date]).

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