Is MGLL p.Pro30Ser (c.88C>T) pathogenic?

MGLL p.Pro30Ser (c.88C>T) is classified Uncertain significance in MGLL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-13). AlphaMissense: likely benign (0.1662); Very rare (popmax 0.00167%, amr).

How common is MGLL p.Pro30Ser (c.88C>T) in the general population?

MGLL p.Pro30Ser (c.88C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about MGLL p.Pro30Ser (c.88C>T)?

AlphaMissense predicts likely benign (score 0.1662) — an in-silico prediction, not a clinical call.

MGLL p.Pro30Ser

c.88C>T · VCV4054526

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1662 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1662	likely benign
REVEL	0.132	moderately benign-leaning
SaProt	LLR -8.57	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 1.3, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 130 kb · p 0.0047 · regional, not allelic
Overall
CADD	18.64	PHRED · no single calibrated threshold — expert panels disagree

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

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P20S vs ClinVar P30S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,012 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000248% 4/1,613,942 alleles · very rare exomes 3/1,461,754 · genomes 1/152,188 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,012
African / African-American	0.00133%	74,928
European (non-Finnish)	0.00017%	589,960

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.Pro30Ser
Coding: c.88C>T
MANE Select: NM_007283
Type: single nucleotide variant
Location: chr3:127821761 (GRCh38)
Gene constraint: LOEUF 0.5 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 94.36 · 30 PDB

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

Similar variants

MGLL p.Ala136Thr Uncertain significance ★ ⚠ same type
MGLL p.Ala174Val Uncertain significance ★ ⚠ same type
MGLL p.Ala233Thr Uncertain significance ★ ⚠ same type
MGLL p.Ala305Thr Uncertain significance ★ ⚠ same type
MGLL p.Arg229Trp Uncertain significance ★ ⚠ same type
MGLL p.Arg232His Uncertain significance ★ ⚠ same type
MGLL p.Arg250Cys Uncertain significance ★ ⚠ same type
MGLL p.Arg73Gly 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-pro30ser (accessed [today's date]).

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