Is LMNB2 p.Pro4Ser (c.10C>T) pathogenic?

LMNB2 p.Pro4Ser (c.10C>T) is classified Likely benign in LMNB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-05). AlphaMissense: likely benign (0.0709); Ultra-rare (popmax 0.0767%, eas); Associated with progressive myoclonic epilepsy type 9.

What condition is associated with LMNB2 p.Pro4Ser (c.10C>T)?

LMNB2 p.Pro4Ser (c.10C>T) is associated with progressive myoclonic epilepsy type 9, lipodystrophy, partial, acquired, susceptibility to (ClinVar).

How common is LMNB2 p.Pro4Ser (c.10C>T) in the general population?

LMNB2 p.Pro4Ser (c.10C>T) is ultra-rare (popmax 0.0767%, eas) (gnomAD).

How is Progressive myoclonic epilepsy type 9 inherited?

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

What do computational predictors say about LMNB2 p.Pro4Ser (c.10C>T)?

AlphaMissense predicts likely benign (score 0.0709) — an in-silico prediction, not a clinical call.

LMNB2 p.Pro4Ser

c.10C>T · rs1345951078 · VCV1568994

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0709 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0767%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Conditions

progressive myoclonic epilepsy type 9

Computational evidence

Protein change
AlphaMissense	0.0709	likely benign
SaProt	LLR -6.17	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP -2.3, phastCons 1
Regional constraint	o/e 1.47	unconstrained · MANE · 59 bp · p 0.022 · regional, not allelic
Overall
CADD	19.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; SaProt is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0767% East Asian · 7/9,132 alleles

Filtering AF 0.0359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0255%

Overall 0.000805% 8/994,366 alleles · ultra-rare exomes 4/847,840 · genomes 4/146,526 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0767%	1,305
African / African-American	0.00176%	56,918

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.Pro4Ser
Coding: c.10C>T
MANE Select: NM_032737
dbSNP: rs1345951078
Type: single nucleotide variant
Location: chr19:2456924 (GRCh38)
Gene constraint: LOEUF 0.399 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.82 · 2 PDB
Residue 4: the 'head' region; the 'disordered' 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.Pro4Leu Benign ★ 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-pro4ser (accessed [today's date]).

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