Is GLA p.Phe211fs (c.626_629dup) pathogenic?

GLA p.Phe211fs (c.626629dup) is classified Likely pathogenic in GLA (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-21). Associated with Fabry disease.

What condition is associated with GLA p.Phe211fs (c.626_629dup)?

GLA p.Phe211fs (c.626_629dup) 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.Phe211fs

c.626_629dup · VCV4856605

Likely pathogenic Single submitter

Classification

Likely 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 4 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.9	GERP 1.8, phastCons 1

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

Variant & gene context

Gene: GLA
Protein: p.Phe211fs
Coding: c.626_629dup
MANE Select: NM_000169
Type: Duplication
Location: chrX:101400675 (GRCh38)
Structure: AlphaFold pLDDT 94.45 · 31 PDB
Residue 211: a turn

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.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
GLA p.Cys52fs Pathogenic/Likely pathogenic ★★ same condition
GLA p.Gln357fs Likely pathogenic ★★ same condition
GLA p.Gln99fs 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-phe211fs (accessed [today's date]).

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