Is LMNB2 p.Ser447= (c.1341C>T) pathogenic?

LMNB2 p.Ser447= (c.1341C>T) is classified Likely benign in LMNB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-09). Very rare (popmax 0.00667%, amr); Associated with progressive myoclonic epilepsy type 9.

What condition is associated with LMNB2 p.Ser447= (c.1341C>T)?

LMNB2 p.Ser447= (c.1341C>T) is associated with progressive myoclonic epilepsy type 9, lipodystrophy, partial, acquired, susceptibility to (ClinVar).

How common is LMNB2 p.Ser447= (c.1341C>T) in the general population?

LMNB2 p.Ser447= (c.1341C>T) is very rare (popmax 0.00667%, amr) (gnomAD).

How is Progressive myoclonic epilepsy type 9 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

LMNB2 p.Ser447=

c.1341C>T · rs767447519 · VCV1533107

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Conditions

progressive myoclonic epilepsy type 9

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 -4.5	GERP -3
Overall
CADD	4.829	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/59,932 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00354% 57/1,610,778 alleles · very rare exomes 51/1,458,534 · genomes 6/152,244 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0372%	2,687
Remaining individualsnot grpmax-eligible	0.00802%	12,473
Admixed Americangrpmax	0.00667%	14,983
South Asian	0.00549%	18,209
African / African-American	0.004%	24,975
Finnishnot grpmax-eligible	0.00325%	30,766
European (non-Finnish)	0.00229%	43,687

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: LMNB2
Protein: p.Ser447=
Coding: c.1341C>T
MANE Select: NM_032737
dbSNP: rs767447519
Type: single nucleotide variant
Location: chr19:2433967 (GRCh38)
Gene constraint: LOEUF 0.399 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.82 · 2 PDB
Residue 447: the 'disordered' region; the 'tail' region

Full LMNB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

progressive myoclonic epilepsy type 9 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: lipodystrophy, partial, acquired, susceptibility to

For Progressive myoclonic epilepsy type 9 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

LMNB2 p.Ser447Gly Uncertain significance ★ ⚠ same residue
LMNB2 c.1202+5G>A Uncertain significance ★★ same condition
LMNB2 p.Ala178Thr Uncertain significance ★★ ⚠ same condition
LMNB2 p.Ala299Val Uncertain significance ★★ ⚠ same condition
LMNB2 p.Ala29Pro Uncertain significance ★★ ⚠ same condition
LMNB2 p.Ala567Thr Uncertain significance ★★ ⚠ same condition
LMNB2 p.Arg104Gly Uncertain significance ★★ ⚠ same condition
LMNB2 p.Arg114His Uncertain significance ★★ ⚠ 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/lmnb2-p-ser447 (accessed [today's date]).

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