Is MGAM p.Ala70Ser (c.208G>T) pathogenic?

MGAM p.Ala70Ser (c.208G>T) is classified Likely benign in MGAM (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-24). AlphaMissense: likely benign (0.0654); Absent from gnomAD v4.1.

How common is MGAM p.Ala70Ser (c.208G>T) in the general population?

MGAM p.Ala70Ser (c.208G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MGAM p.Ala70Ser (c.208G>T)?

AlphaMissense predicts likely benign (score 0.0654) — an in-silico prediction, not a clinical call.

MGAM p.Ala70Ser

c.208G>T · VCV3395619

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0654 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0654	likely benign
REVEL	0.067	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.3	GERP -2
Regional constraint	o/e 0.99	unconstrained · MANE · 59 kb · p 0.57 · regional, not allelic
Overall
CADD	0.005	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: MGAM
Protein: p.Ala70Ser
Coding: c.208G>T
MANE Select: NM_001365693
Type: single nucleotide variant
Location: chr7:142008586 (GRCh38)
Gene constraint: LOEUF 0.832 · pLI <0.01 (gnomAD)
Residue 70: the 'disordered' region

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

Similar variants

MGAM p.Glu805Gly Uncertain significance ★★ same type
MGAM p.Pro1471Ser Uncertain significance ★★ ⚠ same type
MGAM p.Ala1296= Likely benign ★★ same type
MGAM p.Glu2536= Benign ★★ same type
MGAM p.Ile2500Val Benign ★★ same type
MGAM p.Phe2443= Benign ★★ same type
MGAM p.Pro1424Thr Benign ★★ same type
MGAM p.Thr1528= Benign ★★ same type

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/mgam-p-ala70ser (accessed [today's date]).

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