Is LMNB2 p.Ser168= (c.504C>T) pathogenic?

LMNB2 p.Ser168= (c.504C>T) is classified Likely benign in LMNB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-21). Ultra-rare (popmax 0.02%, afr); Associated with progressive myoclonic epilepsy type 9.

What condition is associated with LMNB2 p.Ser168= (c.504C>T)?

LMNB2 p.Ser168= (c.504C>T) is associated with progressive myoclonic epilepsy type 9, lipodystrophy, partial, acquired, susceptibility to (ClinVar).

How common is LMNB2 p.Ser168= (c.504C>T) in the general population?

LMNB2 p.Ser168= (c.504C>T) is ultra-rare (popmax 0.02%, 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.Ser168=

c.504C>T · rs750190446 · VCV1594305

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.1	GERP -3.9
Overall
CADD	1.349	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% African / African-American · 15/74,912 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00989%

Overall 0.00198% 32/1,612,414 alleles · ultra-rare exomes 24/1,460,224 · genomes 8/152,190 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.02%	4,994
East Asian	0.0134%	7,481
Admixed American	0.00333%	29,985
South Asian	0.0011%	91,044
European (non-Finnish)	0.000678%	147,483

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.Ser168=
Coding: c.504C>T
MANE Select: NM_032737
dbSNP: rs750190446
Type: single nucleotide variant
Location: chr19:2438429 (GRCh38)
Gene constraint: LOEUF 0.399 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.82 · 2 PDB
Residue 168: the if rod domain; the 'coil 1b' 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.Ser168Asn 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-ser168 (accessed [today's date]).

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