Is GBE1 p.Asp487Tyr (c.1459G>T) pathogenic?

GBE1 p.Asp487Tyr (c.1459G>T) is classified Likely pathogenic in GBE1 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.9221); No allele count reported in gnomAD v4.1 (AN 1,600,582); Associated with cutis laxa, autosomal recessive, type 1B.

What condition is associated with GBE1 p.Asp487Tyr (c.1459G>T)?

GBE1 p.Asp487Tyr (c.1459G>T) is associated with cutis laxa, autosomal recessive, type 1B (ClinVar).

How common is GBE1 p.Asp487Tyr (c.1459G>T) in the general population?

GBE1 p.Asp487Tyr (c.1459G>T) is no allele count reported in gnomAD v4.1 (AN 1,600,582) (gnomAD).

How is Autosomal recessive cutis laxa type 1 inherited?

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

What do computational predictors say about GBE1 p.Asp487Tyr (c.1459G>T)?

AlphaMissense predicts likely pathogenic (score 0.9221) — an in-silico prediction, not a clinical call.

GBE1 p.Asp487Tyr

c.1459G>T · rs2106933976 · VCV1332750

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9221 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,600,582)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cutis laxa, autosomal recessive, type 1B

Computational evidence

Protein change
AlphaMissense	0.9221	likely pathogenic ✓ concordant with ClinVar
REVEL	0.871	moderately pathogenic-leaning
SaProt	LLR -17.58	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 271 kb · p 0.97 · regional, not allelic
Overall
CADD	28.5	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

No allele count reported in gnomAD v4.1 (AN 1,600,582). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GBE1
Protein: p.Asp487Tyr
Coding: c.1459G>T
MANE Select: NM_000158
dbSNP: rs2106933976
Type: single nucleotide variant
Location: chr3:81578084 (GRCh38)
Gene constraint: LOEUF 1.211 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.30 · 3 PDB

Full GBE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cutis laxa, autosomal recessive, type 1B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive cutis laxa type 1 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

GBE1 p.Asp487Gly Uncertain significance ★ ⚠ same residue
GBE1 c.1109-1G>T Likely pathogenic ★★ same type
GBE1 c.1236+1G>A Likely pathogenic ★★ same type
GBE1 c.1336-1G>A Pathogenic/Likely pathogenic ★★ same type
GBE1 c.143+1G>A Pathogenic ★★ same type
GBE1 c.143+2T>C Pathogenic/Likely pathogenic ★★ same type
GBE1 c.144-1G>C Pathogenic/Likely pathogenic ★★ same type
GBE1 c.1618+1G>A Pathogenic/Likely pathogenic ★★ same type

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/gbe1-p-asp487tyr (accessed [today's date]).

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