Is GLS p.Ala51= (c.153C>T) pathogenic?

GLS p.Ala51= (c.153C>T) is classified Likely benign in GLS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-08-14). Ultra-rare (popmax 0.0836%, sas); Associated with GLS-related disorder.

What condition is associated with GLS p.Ala51= (c.153C>T)?

GLS p.Ala51= (c.153C>T) is associated with GLS-related disorder (ClinVar).

How common is GLS p.Ala51= (c.153C>T) in the general population?

GLS p.Ala51= (c.153C>T) is ultra-rare (popmax 0.0836%, sas) (gnomAD).

GLS p.Ala51=

c.153C>T · VCV3358293

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0836%, sas)

Conditions

GLS-related disorder

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 0.13	GERP -0.75, phastCons 0.97
Overall
CADD	14.64	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0836% South Asian · 24/28,722 alleles

Filtering AF 0.0576% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.049%

Overall 0.00208% 26/1,249,870 alleles · ultra-rare exomes 25/1,098,448 · genomes 1/151,422 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0836%	1,197
Remaining individualsnot grpmax-eligible	0.00435%	23,002

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: GLS
Protein: p.Ala51=
Coding: c.153C>T
MANE Select: NM_014905
Type: single nucleotide variant
Location: chr2:190881237 (GRCh38)
Structure: AlphaFold pLDDT 85.66 · 4 PDB
Residue 51: the 'disordered' region

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

Disease context

GLS-related disorder

Similar variants

GLS p.Gln549Ter Pathogenic ★ same condition
GLS c.1650+1116A>C Uncertain significance ★ same condition
GLS p.Pro96Ser Uncertain significance ★ ⚠ same condition
GLS p.Ser77Ala Uncertain significance ⚠ same condition
GLS c.1650+1093A>G Likely benign same condition
GLS c.1650+8A>C Benign same condition
GLS p.Gly42Glu Likely benign same condition
GLS p.His89Pro Benign 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/gls-p-ala51 (accessed [today's date]).

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