Is GM2A p.Ser50Arg (c.150C>G) pathogenic?

GM2A p.Ser50Arg (c.150C>G) is classified Uncertain significance in GM2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). AlphaMissense: ambiguous (0.5431); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with GM2A p.Ser50Arg (c.150C>G)?

GM2A p.Ser50Arg (c.150C>G) is associated with Inborn genetic diseases (ClinVar).

How common is GM2A p.Ser50Arg (c.150C>G) in the general population?

GM2A p.Ser50Arg (c.150C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GM2A p.Ser50Arg (c.150C>G)?

AlphaMissense predicts ambiguous (score 0.5431) — an in-silico prediction, not a clinical call.

GM2A p.Ser50Arg

c.150C>G · VCV4620931

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5431 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5431	ambiguous
REVEL	0.615	indeterminate
SaProt	LLR -10.24	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.2	GERP 1.4, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 14 kb · p 0.75 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GM2A
Protein: p.Ser50Arg
Coding: c.150C>G
MANE Select: NM_000405
Type: single nucleotide variant
Location: chr5:151259823 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 89.10 · 8 PDB
Residue 50: a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GM2A p.Arg169His Uncertain significance ★★ ⚠ same condition
GM2A p.Asp116His Uncertain significance ★★ ⚠ same condition
GM2A p.Ile58Phe Uncertain significance ★★ same condition
GM2A p.Leu4Pro Uncertain significance ★★ ⚠ same condition
GM2A p.Pro61Arg Uncertain significance ★★ ⚠ same condition
GM2A p.Tyr168Cys Uncertain significance ★★ ⚠ same condition
GM2A p.Ala19Gly Uncertain significance ★ ⚠ same condition
GM2A p.Asp37Gly 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-ser50arg (accessed [today's date]).

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