Is GLA p.His186= (c.558C>T) pathogenic?

GLA p.His186= (c.558C>T) is classified Likely benign in GLA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-01). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with GLA p.His186= (c.558C>T)?

GLA p.His186= (c.558C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is GLA p.His186= (c.558C>T) in the general population?

GLA p.His186= (c.558C>T) is absent from gnomAD v4.1 (gnomAD).

GLA p.His186=

c.558C>T · rs2520887651 · VCV3230481

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.34	GERP 1.9, phastCons 0.009
Overall
CADD	3.237	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GLA
Protein: p.His186=
Coding: c.558C>T
MANE Select: NM_000169
dbSNP: rs2520887651
Type: single nucleotide variant
Location: chrX:101400747 (GRCh38)
Structure: AlphaFold pLDDT 94.45 · 31 PDB
Residue 186: an α-helix

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

Similar variants

GLA p.His186Arg Uncertain significance ★ ⚠ same residue
GLA p.His186Gln Uncertain significance ★ ⚠ same residue
GLA p.His186Pro Conflicting classifications of pathogenicity ★ same residue
GLA c.802-2A>T Pathogenic/Likely pathogenic ★★ same condition
GLA p.Ala143Pro Pathogenic/Likely pathogenic ★★ same condition
GLA p.Arg112His Pathogenic/Likely pathogenic ★★ ⚠ same condition
GLA p.Arg112Leu Pathogenic/Likely pathogenic ★★ same condition
GLA p.Arg301Gln 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-his186 (accessed [today's date]).

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