Is MGAM p.Trp129Arg (c.385T>C) pathogenic?

MGAM p.Trp129Arg (c.385T>C) is classified Uncertain significance in MGAM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: likely benign (0.2858); Ultra-rare (popmax 0.0143%, sas).

How common is MGAM p.Trp129Arg (c.385T>C) in the general population?

MGAM p.Trp129Arg (c.385T>C) is ultra-rare (popmax 0.0143%, sas) (gnomAD).

What do computational predictors say about MGAM p.Trp129Arg (c.385T>C)?

AlphaMissense predicts likely benign (score 0.2858) — an in-silico prediction, not a clinical call.

MGAM p.Trp129Arg

c.385T>C · VCV4107327

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2858 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0143%, sas)

Computational evidence

Protein change
AlphaMissense	0.2858	likely benign
REVEL	0.328	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 4.8, phastCons 0.45
Regional constraint	o/e 0.99	unconstrained · MANE · 59 kb · p 0.57 · regional, not allelic
Overall
CADD	19.47	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 0.0143% South Asian · 13/91,092 alleles

Filtering AF 0.00844% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00661%

Overall 0.000992% 16/1,613,626 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0143%	7,007
Remaining individualsnot grpmax-eligible	0.0016%	62,454
European (non-Finnish)	0.00017%	589,859

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.Trp129Arg
Coding: c.385T>C
MANE Select: NM_001365693
Type: single nucleotide variant
Location: chr7:142019256 (GRCh38)
Gene constraint: LOEUF 0.832 · pLI <0.01 (gnomAD)
Residue 129: the p-type 1 domain; a disulfide bond; a β-strand

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-trp129arg (accessed [today's date]).

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