Is GLA p.Ala73fs (c.217_228delinsCAGAGCCA) pathogenic?

GLA p.Ala73fs (c.217228delinsCAGAGCCA) is classified Pathogenic in GLA (ClinVar, Single submitter, 1 submitter; last evaluated 2026-09-08). Associated with Fabry disease.

What condition is associated with GLA p.Ala73fs (c.217_228delinsCAGAGCCA)?

GLA p.Ala73fs (c.217_228delinsCAGAGCCA) is associated with Fabry disease (ClinVar).

How is Fabry disease inherited?

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

GLA p.Ala73fs

c.217_228delinsCAGAGCCA · VCV4974869

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Fabry disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 2 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 3.4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: GLA
Protein: p.Ala73fs
Coding: c.217_228delinsCAGAGCCA
MANE Select: NM_000169
Type: Indel
Location: chrX:101403952 (GRCh38)
Structure: AlphaFold pLDDT 94.45 · 31 PDB
Residue 73: an α-helix

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.Ala73Glu Likely pathogenic ★ same residue
GLA p.Ala73Ser Uncertain significance ★ ⚠ same residue
GLA p.Ala73Val Uncertain significance ★ ⚠ same residue
GLA p.Ala368fs Pathogenic ★★ same condition
GLA p.Asp55_Gln57delinsValCysLeu Pathogenic/Likely pathogenic ★★ same condition
GLA c.195-13_195-12delinsGC Uncertain significance ★★ same condition
GLA p.Arg332Glu Uncertain significance ★★ same condition
GLA c.802-3_804delinsGGCAACTTT 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-ala73fs (accessed [today's date]).

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