Is GLA p.Cys12= (c.36C>T) pathogenic?

GLA p.Cys12= (c.36C>T) is classified Likely benign in GLA (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-01). Very rare (popmax 0.00296%, eas).

How common is GLA p.Cys12= (c.36C>T) in the general population?

GLA p.Cys12= (c.36C>T) is very rare (popmax 0.00296%, eas) (gnomAD).

GLA p.Cys12=

c.36C>T · VCV4822379

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00296%, eas)

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 -0.074	GERP -6.6
Overall
CADD	2.529	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00296% East Asian · 1/33,783 alleles

Overall 8.26e-05% 1/1,209,999 alleles · very rare exomes 0/1,097,676 · genomes 1/112,323 · joint denominator

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.Cys12=
Coding: c.36C>T
MANE Select: NM_000169
Type: single nucleotide variant
Location: chrX:101407868 (GRCh38)
Structure: AlphaFold pLDDT 94.45 · 31 PDB
Residue 12: a UniProt-annotated variant site (in fabryd; has 4% of wild-type activity)

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

Similar variants

GLA p.Cys12Phe Uncertain significance ★★ ⚠ same residue
GLA p.Cys12Ter Pathogenic ★ same residue
GLA p.Cys12_Leu14del Likely pathogenic ★ same residue
GLA p.Cys12_Leu19del Likely pathogenic ★ same residue
GLA p.Cys12fs Pathogenic ★ same residue
GLA p.Cys12_Ala20delinsSer Uncertain significance ★ same residue
GLA c.1000-10G>A Likely pathogenic ★★ same type
GLA c.1000-1G>A Pathogenic ★★ same type

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-cys12 (accessed [today's date]).

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