Is MGAM p.Val592= (c.1776C>T) pathogenic?

MGAM p.Val592= (c.1776C>T) is classified Likely benign in MGAM (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-01). Rare (popmax 0.289%, nfe).

How common is MGAM p.Val592= (c.1776C>T) in the general population?

MGAM p.Val592= (c.1776C>T) is rare (popmax 0.289%, nfe) (gnomAD).

MGAM p.Val592=

c.1776C>T · rs191698936 · VCV2658098

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.289%, nfe)

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 -9.4	GERP -14
Overall
CADD	0.294	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.289% European (non-Finnish) · 3,343/1,157,858 alleles

Filtering AF 0.281% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.277%

Overall 0.245% 3,861/1,573,836 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.329%	304
European (non-Finnish)grpmax	0.289%	346
Remaining individualsnot grpmax-eligible	0.267%	375
South Asian	0.214%	467
Admixed American	0.122%	822
Middle Eastern	0.118%	846
Ashkenazi Jewishnot grpmax-eligible	0.0795%	1,257
Finnishnot grpmax-eligible	0.0665%	1,505
African / African-American	0.0418%	2,394

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val592=
Coding: c.1776C>T
MANE Select: NM_001365693
dbSNP: rs191698936
Type: single nucleotide variant
Location: chr7:142034368 (GRCh38)
Gene constraint: LOEUF 0.832 · pLI <0.01 (gnomAD)
Residue 592: an α-helix; the 'maltase' 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-val592 (accessed [today's date]).

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