Is GLA p.Thr412Asp (c.1234_1235delinsGA) pathogenic?

GLA p.Thr412Asp (c.12341235delinsGA) is classified Conflicting classifications of pathogenicity in GLA (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-07-20). Associated with Fabry disease.

What condition is associated with GLA p.Thr412Asp (c.1234_1235delinsGA)?

GLA p.Thr412Asp (c.1234_1235delinsGA) 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.Thr412Asp

c.1234_1235delinsGA · VCV4723506

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

Conditions

Fabry disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.9	GERP 3.1, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 6,067 bp · p 6.6e-08 · regional, not allelic

Variant & gene context

Gene: GLA
Protein: p.Thr412Asp
Coding: c.1234_1235delinsGA
MANE Select: NM_000169
Type: Indel
Location: chrX:101397864 (GRCh38)
Structure: AlphaFold pLDDT 94.45 · 31 PDB
Residue 412: a β-strand

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.Thr412fs Pathogenic ★★ same residue
GLA p.Thr412Ile Pathogenic/Likely pathogenic ★★ ⚠ same residue
GLA p.Thr412Asn Likely pathogenic ★ same residue
GLA p.Thr412Pro Likely pathogenic ★ same residue
GLA p.Thr412= Likely benign ★ 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

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-thr412asp (accessed [today's date]).

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