Is GLA p.Thr41= (c.123C>T) pathogenic?

GLA p.Thr41= (c.123C>T) is classified Benign/Likely benign in GLA (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-09-08). Ultra-rare (popmax 0.0285%, nfe); Associated with Fabry disease.

What condition is associated with GLA p.Thr41= (c.123C>T)?

GLA p.Thr41= (c.123C>T) is associated with Fabry disease, cardiomyopathy (ClinVar).

How common is GLA p.Thr41= (c.123C>T) in the general population?

GLA p.Thr41= (c.123C>T) is ultra-rare (popmax 0.0285%, nfe) (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.Thr41=

c.123C>T · rs137902198 · VCV222170

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0285%, nfe)

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 1.4	GERP 0.49, phastCons 1
Overall
CADD	7.762	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0285% European (non-Finnish) · 255/894,559 alleles

Filtering AF 0.0256% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0244%

Overall 0.0222% 269/1,209,596 alleles · ultra-rare exomes 251/1,097,415 · genomes 18/112,181 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0285%	3,508
Remaining individualsnot grpmax-eligible	0.0273%	3,659
African / African-American	0.00175%	57,245

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.Thr41=
Coding: c.123C>T
MANE Select: NM_000169
dbSNP: rs137902198
Type: single nucleotide variant
Location: chrX:101407781 (GRCh38)
Structure: AlphaFold pLDDT 94.45 · 31 PDB

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

Also linked: cardiomyopathy

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.Thr41Ser Uncertain significance ★★ ⚠ same residue
GLA p.Thr41Ile Likely pathogenic ★ ⚠ same residue
GLA p.Thr41fs Likely 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-thr41 (accessed [today's date]).

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