Is GLA p.Lys240fs (c.718_719del) pathogenic?

GLA p.Lys240fs (c.718719del) is classified Pathogenic in GLA (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-09-08). Very rare (popmax 0.000112%, nfe); Associated with Fabry disease.

What condition is associated with GLA p.Lys240fs (c.718_719del)?

GLA p.Lys240fs (c.718_719del) is associated with Fabry disease (ClinVar).

How common is GLA p.Lys240fs (c.718_719del) in the general population?

GLA p.Lys240fs (c.718_719del) is very rare (popmax 0.000112%, nfe) (gnomAD).

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.Lys240fs

c.718_719del · rs869312389 · VCV222371

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

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 5 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.8	GERP 0.27, phastCons 0.96

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000112% European (non-Finnish) · 1/891,397 alleles

Overall 8.28e-05% 1/1,207,416 alleles · very rare exomes 1/1,093,569 · genomes 0/113,847 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: GLA
Protein: p.Lys240fs
Coding: c.718_719del
MANE Select: NM_000169
dbSNP: rs869312389
Type: Deletion
Location: chrX:101398867 (GRCh38)
Structure: AlphaFold pLDDT 94.45 · 31 PDB
Residue 240: 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 c.548del Pathogenic ★★ same condition
GLA c.802-3_802-2del Pathogenic ★★ same condition
GLA c.803_806del Pathogenic ★★ same condition
GLA p.Ala190fs Pathogenic ★★ same condition
GLA p.Ala288fs Pathogenic/Likely pathogenic ★★ same condition
GLA p.Ala352fs Pathogenic ★★ same condition
GLA p.Asn355_Ile359del Likely pathogenic ★★ same condition
GLA p.Cys174fs 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-lys240fs (accessed [today's date]).

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