Is GM2A p.Ser32Asn (c.95G>A) pathogenic?

GM2A p.Ser32Asn (c.95G>A) is classified Likely benign in GM2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-16). AlphaMissense: likely benign (0.1227); Ultra-rare (popmax 0.032%, afr); Associated with Inborn genetic diseases.

What condition is associated with GM2A p.Ser32Asn (c.95G>A)?

GM2A p.Ser32Asn (c.95G>A) is associated with Inborn genetic diseases (ClinVar).

How common is GM2A p.Ser32Asn (c.95G>A) in the general population?

GM2A p.Ser32Asn (c.95G>A) is ultra-rare (popmax 0.032%, afr) (gnomAD).

What do computational predictors say about GM2A p.Ser32Asn (c.95G>A)?

AlphaMissense predicts likely benign (score 0.1227) — an in-silico prediction, not a clinical call.

GM2A p.Ser32Asn

c.95G>A · VCV3520793

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1227 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.032%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1227	likely benign
REVEL	0.112	moderately benign-leaning
SaProt	LLR -4.30	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP 0.26, phastCons 0.001
Regional constraint	o/e 1.02	unconstrained · MANE · 14 kb · p 0.75 · regional, not allelic
Overall
CADD	5.882	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

Grpmax group 0.032% African / African-American · 24/74,922 alleles

Filtering AF 0.022% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0187%

Overall 0.00155% 25/1,613,910 alleles · ultra-rare exomes 11/1,461,702 · genomes 14/152,208 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.032%	3,122
South Asian	0.0011%	91,080

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.Ser32Asn
Coding: c.95G>A
MANE Select: NM_000405
Type: single nucleotide variant
Location: chr5:151259768 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 89.10 · 8 PDB

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-ser32asn (accessed [today's date]).

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