Is GLA p.Glu48Asp (c.144G>T) pathogenic?

GLA p.Glu48Asp (c.144G>T) is classified Pathogenic in GLA (ClinVar, Single submitter, 1 submitter; last evaluated 2026-09-08). AlphaMissense: likely pathogenic (0.8379); Absent from gnomAD v4.1; Associated with Fabry disease.

What condition is associated with GLA p.Glu48Asp (c.144G>T)?

GLA p.Glu48Asp (c.144G>T) is associated with Fabry disease (ClinVar).

How common is GLA p.Glu48Asp (c.144G>T) in the general population?

GLA p.Glu48Asp (c.144G>T) is absent from gnomAD v4.1 (gnomAD).

How is Fabry disease inherited?

Typically X-linked dominant, X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about GLA p.Glu48Asp (c.144G>T)?

AlphaMissense predicts likely pathogenic (score 0.8379) — an in-silico prediction, not a clinical call.

GLA p.Glu48Asp

c.144G>T · VCV4087680

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8379 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Fabry disease

Computational evidence

Protein change
AlphaMissense	0.8379	likely pathogenic ✓ concordant with ClinVar
REVEL	0.839	moderately pathogenic-leaning
SaProt	LLR -10.94	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.3	GERP 0.55, phastCons 1
Regional constraint	o/e 0.25	constrained · MANE · 3,899 bp · p 4.8e-07 · regional, not allelic
Overall
CADD	22.7	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: GLA
Protein: p.Glu48Asp
Coding: c.144G>T
MANE Select: NM_000169
Type: single nucleotide variant
Location: chrX:101407760 (GRCh38)
Structure: AlphaFold pLDDT 94.45 · 31 PDB
Residue 48: an α-helix; a UniProt-annotated variant site (in fabryd; loss of enzyme activity)

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

Disease context

Fabry disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Fabry disease (Orphanet):

Inheritance: X-linked dominant, X-linked recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

GLA p.Glu48Ter Pathogenic/Likely pathogenic ★★ same residue
GLA p.Glu48Gly Likely pathogenic ★ ⚠ same residue
GLA p.Glu48Lys Pathogenic ★ same residue
GLA p.Glu48Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
GLA c.1000-10G>A Likely pathogenic ★★ same condition
GLA c.1000-1G>A Pathogenic ★★ same condition
GLA c.1000-1G>C Pathogenic ★★ same condition
GLA c.1023A>C 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/gla-p-glu48asp (accessed [today's date]).

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