Is LMNB2 p.Ser247Arg (c.739A>C) pathogenic?

LMNB2 p.Ser247Arg (c.739A>C) is classified Uncertain significance in LMNB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-11). AlphaMissense: ambiguous (0.4646); Ultra-rare (popmax 0.0113%, nfe); Associated with LMNB2-related disorder.

What condition is associated with LMNB2 p.Ser247Arg (c.739A>C)?

LMNB2 p.Ser247Arg (c.739A>C) is associated with LMNB2-related disorder, progressive myoclonic epilepsy type 9, lipodystrophy, partial, acquired, susceptibility to (ClinVar).

How common is LMNB2 p.Ser247Arg (c.739A>C) in the general population?

LMNB2 p.Ser247Arg (c.739A>C) is ultra-rare (popmax 0.0113%, nfe) (gnomAD).

What do computational predictors say about LMNB2 p.Ser247Arg (c.739A>C)?

AlphaMissense predicts ambiguous (score 0.4646) — an in-silico prediction, not a clinical call.

LMNB2 p.Ser247Arg

c.739A>C · rs149762712 · VCV2142440

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4646 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0113%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

LMNB2-related disorder

Computational evidence

Protein change
AlphaMissense	0.4646	ambiguous
REVEL	0.111	moderately benign-leaning
SaProt	LLR -9.00	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.54	GERP -3.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 7,487 bp · p 0.38 · regional, not allelic
Overall
CADD	21.2	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0113% European (non-Finnish) · 133/1,179,748 alleles

Filtering AF 0.00969% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00905%

Overall 0.00827% 133/1,608,348 alleles · ultra-rare exomes 125/1,456,164 · genomes 8/152,184 · joint denominator

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.Ser247Arg
Coding: c.739A>C
MANE Select: NM_032737
dbSNP: rs149762712
Type: single nucleotide variant
Location: chr19:2435117 (GRCh38)
Gene constraint: LOEUF 0.399 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.82 · 2 PDB
Residue 247: the if rod domain; the 'linker 2' region

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

Disease context

LMNB2-related disorder

Also linked: progressive myoclonic epilepsy type 9 lipodystrophy, partial, acquired, susceptibility to

Similar variants

LMNB2 p.Glu398Lys Pathogenic ★★ same condition
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-ser247arg (accessed [today's date]).

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