Is LMNB2 p.Pro543= (c.1629C>T) pathogenic?

LMNB2 p.Pro543= (c.1629C>T) is classified Likely benign in LMNB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-05-01). Ultra-rare (popmax 0.0587%, afr); Associated with lipodystrophy, partial, acquired, susceptibility to.

How common is LMNB2 p.Pro543= (c.1629C>T) in the general population?

LMNB2 p.Pro543= (c.1629C>T) is ultra-rare (popmax 0.0587%, afr) (gnomAD).

LMNB2 p.Pro543=

Q: What condition is associated with LMNB2 p.Pro543= (c.1629C>T)?

LMNB2 p.Pro543= (c.1629C>T) is associated with lipodystrophy, partial, acquired, susceptibility to, progressive myoclonic epilepsy type 9 (ClinVar).

c.1629C>T · rs149126950 · VCV1088110

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0587%, afr)

Conditions

lipodystrophy, partial, acquired, susceptibility to

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 -6.9	GERP -3.8
Overall
CADD	0.265	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0587% African / African-American · 44/75,020 alleles

Filtering AF 0.0448% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.04%

Overall 0.00329% 53/1,612,892 alleles · ultra-rare exomes 26/1,460,664 · genomes 27/152,228 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0587%	1,705
Remaining individualsnot grpmax-eligible	0.0048%	20,819
Finnishnot grpmax-eligible	0.00317%	31,555
European (non-Finnish)	0.000339%	294,964

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.Pro543=
Coding: c.1629C>T
MANE Select: NM_032737
dbSNP: rs149126950
Type: single nucleotide variant
Location: chr19:2431864 (GRCh38)
Gene constraint: LOEUF 0.399 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.82 · 2 PDB
Residue 543: the 'tail' region; the ltd domain; a turn

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

Disease context

lipodystrophy, partial, acquired, susceptibility to — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: progressive myoclonic epilepsy type 9

Similar variants

LMNB2 p.Pro543Arg 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-pro543 (accessed [today's date]).

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