Is MGLL p.Ser291= (c.873C>T) pathogenic?

MGLL p.Ser291= (c.873C>T) is classified Likely benign in MGLL (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-01). Ultra-rare (popmax 0.0135%, nfe); Associated with MGLL-related disorder.

What condition is associated with MGLL p.Ser291= (c.873C>T)?

MGLL p.Ser291= (c.873C>T) is associated with MGLL-related disorder (ClinVar).

How common is MGLL p.Ser291= (c.873C>T) in the general population?

MGLL p.Ser291= (c.873C>T) is ultra-rare (popmax 0.0135%, nfe) (gnomAD).

MGLL p.Ser291=

c.873C>T · rs748034490 · VCV3043265

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0135%, nfe)

Conditions

MGLL-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.037	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.7	GERP -4.3
Overall
CADD	1.005	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0135% European (non-Finnish) · 159/1,179,896 alleles

Filtering AF 0.0117% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0111%

Overall 0.0108% 175/1,613,864 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0135%	7,421
Remaining individualsnot grpmax-eligible	0.0128%	7,810
African / African-American	0.00668%	14,980
Admixed American	0.00333%	30,001
South Asian	0.0011%	91,088

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: MGLL
Protein: p.Ser291=
Coding: c.873C>T
MANE Select: NM_007283
dbSNP: rs748034490
Type: single nucleotide variant
Location: chr3:127692267 (GRCh38)
Gene constraint: LOEUF 0.5 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 94.36 · 30 PDB
Residue 291: an α-helix

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

Disease context

MGLL-related disorder

Similar variants

MGLL c.155+7C>G Likely benign same condition
MGLL p.Ala307Thr Likely benign same condition
MGLL p.Gly220Ser Likely benign ⚠ same condition
MGLL p.His85= Benign same condition
MGLL p.Leu251= Benign same condition
MGLL p.Val107Ile Likely benign same condition
MGLL p.Ala136Thr Uncertain significance ★ ⚠ same type
MGLL p.Ala174Val Uncertain significance ★ ⚠ 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/mgll-p-ser291 (accessed [today's date]).

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