Is GLA p.Lys213fs (c.638del) pathogenic?

GLA p.Lys213fs (c.638del) is classified Likely pathogenic in GLA (ClinVar, Single submitter, 1 submitter; last evaluated 2026-09-08). Very rare (popmax 0.0018%, afr); Associated with Fabry disease.

What condition is associated with GLA p.Lys213fs (c.638del)?

GLA p.Lys213fs (c.638del) is associated with Fabry disease (ClinVar).

How common is GLA p.Lys213fs (c.638del) in the general population?

GLA p.Lys213fs (c.638del) is very rare (popmax 0.0018%, afr) (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.Lys213fs

c.638del · VCV4086987

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0018%, afr)

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 7.7	GERP 2.7, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0018% African / African-American · 1/55,693 alleles

Filtering AF 4.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.6e-05%

Overall 0.000271% 3/1,108,991 alleles · very rare exomes 3/996,040 · genomes 0/112,951 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0018%	55,693
European (non-Finnish)	0.000249%	401,349

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.Lys213fs
Coding: c.638del
MANE Select: NM_000169
Type: Deletion
Location: chrX:101400667 (GRCh38)
Structure: AlphaFold pLDDT 94.45 · 31 PDB
Residue 213: a UniProt-annotated variant site (in fabryd; uncertain significance; decreased enzyme activity)

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.Lys213Asn Pathogenic ★ ⚠ same residue
GLA p.Lys213Arg Uncertain significance ★ ⚠ same residue
GLA p.Lys213Met Uncertain significance ★ ⚠ same residue
GLA p.Lys213Thr Uncertain significance ★ ⚠ same residue
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

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-lys213fs (accessed [today's date]).

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