Is GLA p.Pro110= (c.330T>G) pathogenic?

GLA p.Pro110= (c.330T>G) is classified Likely benign in GLA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-09). Very rare (popmax 0.00175%, sas); Associated with Cardiovascular phenotype.

What condition is associated with GLA p.Pro110= (c.330T>G)?

GLA p.Pro110= (c.330T>G) is associated with Cardiovascular phenotype, Fabry disease (ClinVar).

How common is GLA p.Pro110= (c.330T>G) in the general population?

GLA p.Pro110= (c.330T>G) is very rare (popmax 0.00175%, sas) (gnomAD).

GLA p.Pro110=

c.330T>G · rs781967285 · VCV222215

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00175%, sas)

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 2.1	GERP 2.3, phastCons 0.84
Overall
CADD	9.287	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00175% South Asian · 1/57,046 alleles

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

Overall 0.000248% 3/1,211,790 alleles · very rare exomes 3/1,097,625 · genomes 0/114,165 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00175%	57,046
European (non-Finnish)	0.000223%	447,547

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.Pro110=
Coding: c.330T>G
MANE Select: NM_000169
dbSNP: rs781967285
Type: single nucleotide variant
Location: chrX:101403850 (GRCh38)
Structure: AlphaFold pLDDT 94.45 · 31 PDB
Residue 110: a turn

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.Pro110Arg Uncertain significance ★ ⚠ same residue
GLA p.Pro110Leu Uncertain significance ★ ⚠ same residue
GLA p.Pro110fs 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

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-pro110 (accessed [today's date]).

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