Is GM2A p.Leu93Phe (c.276_277delinsTT) pathogenic?

GM2A p.Leu93Phe (c.276277delinsTT) is classified Uncertain significance in GM2A (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-20). No gnomAD frequency available for this variant; Associated with Tay-Sachs disease AB variant.

What condition is associated with GM2A p.Leu93Phe (c.276_277delinsTT)?

GM2A p.Leu93Phe (c.276_277delinsTT) is associated with Tay-Sachs disease AB variant (ClinVar).

How common is GM2A p.Leu93Phe (c.276_277delinsTT) in the general population?

GM2A p.Leu93Phe (c.276_277delinsTT) is no gnomAD frequency available for this variant (gnomAD).

How is GM2 gangliosidosis, AB variant inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

GM2A p.Leu93Phe

c.276_277delinsTT · rs1753894633 · VCV1040377

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Tay-Sachs disease AB variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.58	GERP 0.74
Regional constraint	o/e 1.02	unconstrained · MANE · 14 kb · p 0.75 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GM2A
Protein: p.Leu93Phe
Coding: c.276_277delinsTT
MANE Select: NM_000405
dbSNP: rs1753894633
Type: Indel
Location: chr5:151266763 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 89.10 · 8 PDB
Residue 93: a β-strand

Full GM2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Tay-Sachs disease AB variant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For GM2 gangliosidosis, AB variant (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

GM2A p.Leu93Arg Uncertain significance ★ same residue
GM2A p.Met69Ala Uncertain significance ★ same condition
GM2A p.Cys112fs Pathogenic ★★ same condition
GM2A p.Glu123fs Likely pathogenic ★★ same condition
GM2A c.*356C>A Uncertain significance ★★ same condition
GM2A c.*724G>C Uncertain significance ★★ same condition
GM2A p.Ala188Gly Uncertain significance ★★ ⚠ same condition
GM2A p.Arg169His Uncertain significance ★★ ⚠ 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/gm2a-p-leu93phe (accessed [today's date]).

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