Is MGAM p.Phe899= (c.2697T>C) pathogenic?

MGAM p.Phe899= (c.2697T>C) is classified Likely benign in MGAM (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-09-12). Rare (popmax 0.145%, amr); Associated with MGAM-related disorder.

What condition is associated with MGAM p.Phe899= (c.2697T>C)?

MGAM p.Phe899= (c.2697T>C) is associated with MGAM-related disorder (ClinVar).

How common is MGAM p.Phe899= (c.2697T>C) in the general population?

MGAM p.Phe899= (c.2697T>C) is rare (popmax 0.145%, amr) (gnomAD).

MGAM p.Phe899=

c.2697T>C · VCV3344078

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.145%, amr)

Conditions

MGAM-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP 0.77, phastCons 1
Overall
CADD	1.994	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.145% Admixed American · 87/60,006 alleles

Filtering AF 0.12% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.111%

Overall 0.00899% 145/1,613,798 alleles · rare exomes 110/1,461,464 · genomes 35/152,334 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.145%	690
African / African-American	0.0426%	2,345
Middle Eastern	0.033%	3,030
Remaining individualsnot grpmax-eligible	0.0032%	31,238
South Asian	0.0022%	45,531
European (non-Finnish)	0.0017%	58,987

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.Phe899=
Coding: c.2697T>C
MANE Select: NM_001365693
Type: single nucleotide variant
Location: chr7:142050756 (GRCh38)
Gene constraint: LOEUF 0.832 · pLI <0.01 (gnomAD)
Residue 899: a β-strand

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

Disease context

MGAM-related disorder

Similar variants

MGAM p.Glu805Gly Uncertain significance ★★ same condition
MGAM p.Gly2312Val Uncertain significance ★ same condition
MGAM p.Ile609Ser Uncertain significance ★ ⚠ same condition
MGAM p.Tyr1044Ter Uncertain significance ★ same condition
MGAM c.2374-4T>A Likely benign same condition
MGAM c.4122+1G>T Likely benign same condition
MGAM c.5186+5A>G Likely benign same condition
MGAM c.7608-8C>T Likely benign 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/mgam-p-phe899 (accessed [today's date]).

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