Is GLA p.Thr282fs (c.842dup) pathogenic?

GLA p.Thr282fs (c.842dup) is classified Pathogenic in GLA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-14). Absent from gnomAD; Associated with Fabry disease.

What condition is associated with GLA p.Thr282fs (c.842dup)?

GLA p.Thr282fs (c.842dup) is associated with Fabry disease (ClinVar).

How common is GLA p.Thr282fs (c.842dup) in the general population?

GLA p.Thr282fs (c.842dup) is absent from gnomAD (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.Thr282fs

c.842dup · rs2520864097 · VCV2022103

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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	predicted	premature termination codon in exon 6 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.5	GERP 2, 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.Thr282fs
Coding: c.842dup
MANE Select: NM_000169
dbSNP: rs2520864097
Type: Duplication
Location: chrX:101398526 (GRCh38)
Structure: AlphaFold pLDDT 94.45 · 31 PDB
Residue 282: 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.Thr282Ala Likely pathogenic ★ ⚠ same residue
GLA p.Thr282Ile Likely pathogenic ★ same residue
GLA p.Thr282Pro Likely pathogenic ★ same residue
GLA p.Thr282Asn Conflicting classifications of pathogenicity ★ ⚠ 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

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-thr282fs (accessed [today's date]).

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