Is GLA p.Ile319fs (c.950_954dup) pathogenic?

GLA p.Ile319fs (c.950954dup) is classified Pathogenic/Likely pathogenic in GLA (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-09-08). No gnomAD frequency available for this variant; Associated with Fabry disease.

What condition is associated with GLA p.Ile319fs (c.950_954dup)?

GLA p.Ile319fs (c.950_954dup) is associated with Fabry disease (ClinVar).

How common is GLA p.Ile319fs (c.950_954dup) in the general population?

GLA p.Ile319fs (c.950_954dup) is no gnomAD frequency available for this variant (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.Ile319fs

c.950_954dup · rs1603038220 · VCV10752

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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	escapes	premature termination codon within the last 50 nt of the penultimate exon (6 of 7, 44 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.3	GERP 2.3, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: GLA
Protein: p.Ile319fs
Coding: c.950_954dup
MANE Select: NM_000169
dbSNP: rs1603038220
Type: Duplication
Location: chrX:101398414 (GRCh38)
Structure: AlphaFold pLDDT 94.45 · 31 PDB
Residue 319: a UniProt-annotated variant site (in fabryd); 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.Ile319Phe Likely pathogenic ★ same residue
GLA p.Ile319Thr Likely pathogenic ★ same residue
GLA p.Ile319= Likely benign ★ same residue
GLA c.801+2dup Pathogenic ★★ same condition
GLA p.Ala348fs Pathogenic ★★ same condition
GLA p.Asn139fs Pathogenic/Likely pathogenic ★★ same condition
GLA p.Asn355fs Pathogenic/Likely pathogenic ★★ same condition
GLA p.Asp93Ter 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-ile319fs (accessed [today's date]).

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