Is MGLL p.Ser16Phe (c.47C>T) pathogenic?

MGLL p.Ser16Phe (c.47C>T) is classified Benign in MGLL (ClinVar, Single submitter, 2 submitters; last evaluated 2023-11-01). AlphaMissense: likely benign (0.1161); Rare (popmax 0.181%, mid).

How common is MGLL p.Ser16Phe (c.47C>T) in the general population?

MGLL p.Ser16Phe (c.47C>T) is rare (popmax 0.181%, mid) (gnomAD).

What do computational predictors say about MGLL p.Ser16Phe (c.47C>T)?

AlphaMissense predicts likely benign (score 0.1161) — an in-silico prediction, not a clinical call.

MGLL p.Ser16Phe

c.47C>T · rs201175620 · VCV2672955

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1161 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.181%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1161	likely benign
REVEL	0.224	benign-leaning
SaProt	LLR -9.07	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 5	GERP -0.74, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 130 kb · p 0.0047 · regional, not allelic
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S6F vs ClinVar S16F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.181% Middle Eastern · 11/6,062 alleles

Filtering AF 0.102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0838%

Overall 0.0797% 1,286/1,614,118 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	2.17%	46
Remaining individualsnot grpmax-eligible	0.29%	345
Middle Easterngrpmax	0.181%	551
Admixed American	0.113%	883
European (non-Finnish)	0.0314%	3,181
African / African-American	0.0147%	6,821
East Asian	0.00223%	44,878
South Asian	0.0022%	45,538

Ashkenazi Jewish 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: MGLL
Protein: p.Ser16Phe
Coding: c.47C>T
MANE Select: NM_007283
dbSNP: rs201175620
Type: single nucleotide variant
Location: chr3:127821802 (GRCh38)
Gene constraint: LOEUF 0.5 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 94.36 · 30 PDB
Residue 16: an α-helix

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-ser16phe (accessed [today's date]).

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