Is GLA p.Asp315= (c.945C>T) pathogenic?

GLA p.Asp315= (c.945C>T) is classified Conflicting classifications of pathogenicity in GLA (ClinVar, Conflicting submitters, 19 submitters; last evaluated 2026-09-08). Ultra-rare (popmax 0.033%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with GLA p.Asp315= (c.945C>T)?

GLA p.Asp315= (c.945C>T) is associated with Cardiovascular phenotype, Fabry disease (ClinVar).

How common is GLA p.Asp315= (c.945C>T) in the general population?

GLA p.Asp315= (c.945C>T) is ultra-rare (popmax 0.033%, nfe) (gnomAD).

GLA p.Asp315=

c.945C>T · rs151208856 · VCV42465

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 19 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.86 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.9	GERP -0.16, phastCons 1
Overall
CADD	6.93	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% European (non-Finnish) · 295/893,618 alleles

Filtering AF 0.0299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0287%

Overall 0.0257% 311/1,207,797 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.033%	3,029
Remaining individualsnot grpmax-eligible	0.0168%	5,939
Admixed American	0.011%	9,131
African / African-American	0.00351%	28,506
South Asian	0.00176%	56,730

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.Asp315=
Coding: c.945C>T
MANE Select: NM_000169
dbSNP: rs151208856
Type: single nucleotide variant
Location: chrX:101398424 (GRCh38)
Structure: AlphaFold pLDDT 94.45 · 31 PDB
Residue 315: a UniProt-annotated variant site (in fabryd; uncertain significance; decreased enzyme activity); 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

Also linked: Fabry disease

Similar variants

GLA p.Asp315Asn Uncertain significance ★ ⚠ same residue
GLA p.Asp315_Val316insTer Pathogenic ★ same residue
GLA c.1000-10G>A Likely pathogenic ★★ same condition
GLA c.1000-1G>A Pathogenic ★★ same condition
GLA c.1000-1G>C Pathogenic ★★ same condition
GLA c.1023A>C Pathogenic/Likely pathogenic ★★ ⚠ same condition
GLA c.194+1G>A Pathogenic ★★ same condition
GLA c.194+1G>T 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-asp315 (accessed [today's date]).

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