Is MGAM p.Arg1304Pro (c.3911G>C) pathogenic?

MGAM p.Arg1304Pro (c.3911G>C) is classified Uncertain significance in MGAM (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-28). AlphaMissense: likely pathogenic (0.9299); Very rare (popmax 8.48e-05%, nfe).

How common is MGAM p.Arg1304Pro (c.3911G>C) in the general population?

MGAM p.Arg1304Pro (c.3911G>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about MGAM p.Arg1304Pro (c.3911G>C)?

AlphaMissense predicts likely pathogenic (score 0.9299) — an in-silico prediction, not a clinical call.

MGAM p.Arg1304Pro

c.3911G>C · rs769721754 · VCV2298228

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9299 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.9299	likely pathogenic · top 9% in MGAM
REVEL	0.663	pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 3.9, phastCons 0.38
Regional constraint	o/e 0.99	unconstrained · MANE · 59 kb · p 0.57 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,040 alleles

Overall 0.000657% 1/152,126 alleles · very rare

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: MGAM
Protein: p.Arg1304Pro
Coding: c.3911G>C
MANE Select: NM_001365693
dbSNP: rs769721754
Type: single nucleotide variant
Location: chr7:142059563 (GRCh38)
Gene constraint: LOEUF 0.832 · pLI <0.01 (gnomAD)
Residue 1304: the 'glucoamylase' region

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

Similar variants

MGAM p.Arg1304Cys Uncertain significance ★ same residue
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

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-arg1304pro (accessed [today's date]).

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