Is GLA p.Asp33Asn (c.97G>A) pathogenic?

GLA p.Asp33Asn (c.97G>A) is classified Uncertain significance in GLA (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely benign (0.1057); Absent from gnomAD v4.1.

How common is GLA p.Asp33Asn (c.97G>A) in the general population?

GLA p.Asp33Asn (c.97G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GLA p.Asp33Asn (c.97G>A)?

AlphaMissense predicts likely benign (score 0.1057) — an in-silico prediction, not a clinical call.

GLA p.Asp33Asn

c.97G>A · rs2147487414 · VCV1049385

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1057 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1057	likely benign
REVEL	0.491	indeterminate
SaProt	LLR -6.80	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.006	GERP 1.6, phastCons 0.78
Regional constraint	o/e 0.93	unconstrained · MANE · 123 bp · p 0.7 · regional, not allelic
Overall
CADD	13.85	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Asp33Asn
Coding: c.97G>A
MANE Select: NM_000169
dbSNP: rs2147487414
Type: single nucleotide variant
Location: chrX:101407807 (GRCh38)
Structure: AlphaFold pLDDT 94.45 · 31 PDB
Residue 33: a UniProt-annotated variant site (in fabryd; uncertain significance; decreased enzyme activity)

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

Similar variants

GLA p.Asp33Gly Likely pathogenic ★ ⚠ same residue
GLA p.Asp33His Likely pathogenic ★ ⚠ same residue
GLA p.Asp33Tyr Likely pathogenic ★ ⚠ same residue
GLA p.Asp33Glu Uncertain significance ★ ⚠ same residue
GLA c.1000-10G>A Likely pathogenic ★★ same type
GLA c.1000-1G>A Pathogenic ★★ same type
GLA c.1000-1G>C Pathogenic ★★ same type
GLA c.1023A>C Pathogenic/Likely 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-asp33asn (accessed [today's date]).

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