Is GLA p.Tyr397= (c.1191T>C) pathogenic?

GLA p.Tyr397= (c.1191T>C) is classified Likely benign in GLA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-08-25). Very rare (popmax 0.00218%, amr); Associated with Fabry disease.

What condition is associated with GLA p.Tyr397= (c.1191T>C)?

GLA p.Tyr397= (c.1191T>C) is associated with Fabry disease (ClinVar).

How common is GLA p.Tyr397= (c.1191T>C) in the general population?

GLA p.Tyr397= (c.1191T>C) is very rare (popmax 0.00218%, amr) (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.Tyr397=

c.1191T>C · rs869312236 · VCV222156

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00218%, amr)

Conditions

Fabry disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP 2.1, phastCons 0.44
Overall
CADD	6.026	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00218% Admixed American · 1/45,896 alleles

Overall 0.000166% 2/1,208,439 alleles · very rare exomes 1/1,095,452 · genomes 1/112,987 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00218%	45,896
European (non-Finnish)	0.000112%	892,969

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.Tyr397=
Coding: c.1191T>C
MANE Select: NM_000169
dbSNP: rs869312236
Type: single nucleotide variant
Location: chrX:101397908 (GRCh38)
Structure: AlphaFold pLDDT 94.45 · 31 PDB
Residue 397: 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.Tyr397Ter Pathogenic ★ same residue
GLA p.Tyr397Cys Uncertain significance ★ ⚠ same residue
GLA p.Tyr397fs Pathogenic ★★ same residue
GLA c.1000-10G>A Likely pathogenic ★★ same condition
GLA c.1000-1G>A Pathogenic ★★ same condition
GLA c.1000-1G>C Pathogenic ★★ same condition
GLA c.1023A>C Pathogenic/Likely pathogenic ★★ ⚠ same condition
GLA c.194+1G>A 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-tyr397 (accessed [today's date]).

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