Is LMNB2 p.Pro449= (c.1347A>C) pathogenic?

LMNB2 p.Pro449= (c.1347A>C) is classified Likely benign in LMNB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-23). Very rare (popmax 0.00133%, afr); Associated with progressive myoclonic epilepsy type 9.

What condition is associated with LMNB2 p.Pro449= (c.1347A>C)?

LMNB2 p.Pro449= (c.1347A>C) is associated with progressive myoclonic epilepsy type 9, lipodystrophy, partial, acquired, susceptibility to (ClinVar).

How common is LMNB2 p.Pro449= (c.1347A>C) in the general population?

LMNB2 p.Pro449= (c.1347A>C) is very rare (popmax 0.00133%, afr) (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.Pro449=

c.1347A>C · VCV3760416

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.6	GERP -2.5
Overall
CADD	0.282	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,918 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,611,302 alleles · very rare exomes 3/1,459,090 · genomes 1/152,212 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,918
European (non-Finnish)	0.000254%	393,204

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.Pro449=
Coding: c.1347A>C
MANE Select: NM_032737
Type: single nucleotide variant
Location: chr19:2433961 (GRCh38)
Gene constraint: LOEUF 0.399 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.82 · 2 PDB
Residue 449: 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 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
LMNB2 p.Arg148Cys 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-pro449 (accessed [today's date]).

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