Is GLA p.Cys142= (c.426C>T) pathogenic?

GLA p.Cys142= (c.426C>T) is classified Likely benign in GLA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-03). Ultra-rare (popmax 0.0458%, mid); Associated with Cardiovascular phenotype.

What condition is associated with GLA p.Cys142= (c.426C>T)?

GLA p.Cys142= (c.426C>T) is associated with Cardiovascular phenotype, Fabry disease (ClinVar).

How common is GLA p.Cys142= (c.426C>T) in the general population?

GLA p.Cys142= (c.426C>T) is ultra-rare (popmax 0.0458%, mid) (gnomAD).

GLA p.Cys142=

c.426C>T · rs1421866281 · VCV1115175

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0458%, mid)

Conditions

Cardiovascular phenotype

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 -1.3	GERP -0.75
Overall
CADD	2.034	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0458% Middle Eastern · 2/4,366 alleles

Filtering AF 0.0081% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00339%

Overall 0.00116% 14/1,208,505 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0458%	2,183
Admixed American	0.00437%	22,883
South Asian	0.00352%	28,406
European (non-Finnish)	0.000895%	111,715

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.Cys142=
Coding: c.426C>T
MANE Select: NM_000169
dbSNP: rs1421866281
Type: single nucleotide variant
Location: chrX:101401753 (GRCh38)
Structure: AlphaFold pLDDT 94.45 · 31 PDB
Residue 142: a disulfide bond; a UniProt-annotated variant site (in fabryd)

Full GLA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Fabry disease

Similar variants

GLA p.Cys142Ter Pathogenic ★★ same residue
GLA p.Cys142Phe Likely pathogenic ★ same residue
GLA p.Cys142Trp Pathogenic ★ same residue
GLA p.Cys142Tyr 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

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-cys142 (accessed [today's date]).

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