Is GM2A p.Val114= (c.342G>C) pathogenic?

GM2A p.Val114= (c.342G>C) is classified Likely benign in GM2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-18). Very rare (popmax 0.00133%, afr); Associated with Tay-Sachs disease AB variant.

What condition is associated with GM2A p.Val114= (c.342G>C)?

GM2A p.Val114= (c.342G>C) is associated with Tay-Sachs disease AB variant (ClinVar).

How common is GM2A p.Val114= (c.342G>C) in the general population?

GM2A p.Val114= (c.342G>C) is very rare (popmax 0.00133%, afr) (gnomAD).

How is GM2 gangliosidosis, AB variant inherited?

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

GM2A p.Val114=

c.342G>C · rs777250593 · VCV2159623

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

Tay-Sachs disease AB variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.031	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.27	GERP -2.1
Overall
CADD	0.369	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,040 alleles

Overall 6.2e-05% 1/1,613,870 alleles · very rare exomes 1/1,461,590 · genomes 0/152,280 · joint denominator

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: GM2A
Protein: p.Val114=
Coding: c.342G>C
MANE Select: NM_000405
dbSNP: rs777250593
Type: single nucleotide variant
Location: chr5:151266829 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 89.10 · 8 PDB
Residue 114: an α-helix

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 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
GM2A p.Arg169Ser Uncertain significance ★★ ⚠ same condition
GM2A p.Arg180His Uncertain significance ★★ ⚠ same condition
GM2A p.Arg180Ser Uncertain significance ★★ ⚠ same condition
GM2A p.Asp116His 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-val114 (accessed [today's date]).

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