Is GLA p.Lys326= (c.978G>A) pathogenic?

GLA p.Lys326= (c.978G>A) is classified Benign/Likely benign in GLA (ClinVar, Multiple submitters, 17 submitters; last evaluated 2026-02-01). Rare (popmax 0.284%, afr); Associated with Cardiovascular phenotype.

What condition is associated with GLA p.Lys326= (c.978G>A)?

GLA p.Lys326= (c.978G>A) is associated with Cardiovascular phenotype, Fabry disease (ClinVar).

How common is GLA p.Lys326= (c.978G>A) in the general population?

GLA p.Lys326= (c.978G>A) is rare (popmax 0.284%, afr) (gnomAD).

GLA p.Lys326=

c.978G>A · rs151195362 · VCV42466

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 17 submitters

gnomAD v4.1

Rare

rare (popmax 0.284%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP 2.5, phastCons 1
Overall
CADD	6.943	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.284% African / African-American · 162/57,034 alleles

Filtering AF 0.248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.235%

Overall 0.0171% 206/1,204,535 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.284%	352
Admixed American	0.0504%	1,986
Remaining individualsnot grpmax-eligible	0.0379%	2,635
Middle Eastern	0.0232%	4,312
South Asian	0.00353%	28,336

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.Lys326=
Coding: c.978G>A
MANE Select: NM_000169
dbSNP: rs151195362
Type: single nucleotide variant
Location: chrX:101398391 (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

Also linked: Fabry disease

Similar variants

GLA p.Lys326fs 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
GLA c.195-1G>C 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-lys326 (accessed [today's date]).

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