Is GLA p.His9Arg (c.26A>G) pathogenic?

GLA p.His9Arg (c.26A>G) is classified Conflicting classifications of pathogenicity in GLA (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-09-29). AlphaMissense: likely benign (0.0462); Very rare (popmax 0.000224%, nfe); Associated with Fabry disease.

What condition is associated with GLA p.His9Arg (c.26A>G)?

GLA p.His9Arg (c.26A>G) is associated with Fabry disease (ClinVar).

How common is GLA p.His9Arg (c.26A>G) in the general population?

GLA p.His9Arg (c.26A>G) is very rare (popmax 0.000224%, 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.

What do computational predictors say about GLA p.His9Arg (c.26A>G)?

AlphaMissense predicts likely benign (score 0.0462) — an in-silico prediction, not a clinical call.

GLA p.His9Arg

c.26A>G · rs1555987214 · VCV870773

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0462 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000224%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Fabry disease

Computational evidence

Protein change
AlphaMissense	0.0462	likely benign
REVEL	0.221	benign-leaning
SaProt	LLR -4.65	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -3.4	GERP -3.6
Regional constraint	o/e 0.93	unconstrained · MANE · 123 bp · p 0.7 · regional, not allelic
Overall
CADD	0.013	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000224% European (non-Finnish) · 2/894,173 alleles

Filtering AF 3.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000165% 2/1,209,106 alleles · very rare exomes 1/1,096,890 · genomes 1/112,216 · 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.His9Arg
Coding: c.26A>G
MANE Select: NM_000169
dbSNP: rs1555987214
Type: single nucleotide variant
Location: chrX:101407878 (GRCh38)

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)

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-his9arg (accessed [today's date]).

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