Is GLA p.Gln2Leu (c.5A>T) pathogenic?

GLA p.Gln2Leu (c.5A>T) is classified Likely benign in GLA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-21). AlphaMissense: likely benign (0.082); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with GLA p.Gln2Leu (c.5A>T)?

GLA p.Gln2Leu (c.5A>T) is associated with Cardiovascular phenotype (ClinVar).

How common is GLA p.Gln2Leu (c.5A>T) in the general population?

GLA p.Gln2Leu (c.5A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GLA p.Gln2Leu (c.5A>T)?

AlphaMissense predicts likely benign (score 0.082) — an in-silico prediction, not a clinical call.

GLA p.Gln2Leu

c.5A>T · rs782386191 · VCV3230482

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.082 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.082	likely benign
REVEL	0.18	moderately benign-leaning
SaProt	LLR -4.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.5	GERP -2.6
Regional constraint	o/e 0.93	unconstrained · MANE · 123 bp · p 0.7 · regional, not allelic
Overall
CADD	5.89	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

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.Gln2Leu
Coding: c.5A>T
MANE Select: NM_000169
dbSNP: rs782386191
Type: single nucleotide variant
Location: chrX:101407899 (GRCh38)
Structure: AlphaFold pLDDT 94.45 · 31 PDB

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.Gln2Ter Pathogenic ★★ same residue
GLA p.Gln2Arg Uncertain significance ★★ ⚠ same residue
GLA p.Gln2Pro Uncertain significance ★★ ⚠ same residue
GLA p.Gln2= Likely benign ★★ same residue
GLA p.Gln2His Uncertain significance ★ ⚠ 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

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-gln2leu (accessed [today's date]).

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