Is LMNB2 p.Val84= (c.252G>C) pathogenic?

LMNB2 p.Val84= (c.252G>C) is classified Likely benign in LMNB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-02). Very rare (popmax 0.00235%, nfe); Associated with lipodystrophy, partial, acquired, susceptibility to.

What condition is associated with LMNB2 p.Val84= (c.252G>C)?

LMNB2 p.Val84= (c.252G>C) is associated with lipodystrophy, partial, acquired, susceptibility to, progressive myoclonic epilepsy type 9 (ClinVar).

How common is LMNB2 p.Val84= (c.252G>C) in the general population?

LMNB2 p.Val84= (c.252G>C) is very rare (popmax 0.00235%, nfe) (gnomAD).

LMNB2 p.Val84=

c.252G>C · rs1972094753 · VCV1104013

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00235%, nfe)

Conditions

lipodystrophy, partial, acquired, susceptibility to

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.73	donor loss · deltas
Constraint at this position
Conservation	phyloP 2.4	GERP 0.8, phastCons 1
Overall
CADD	12.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00235% European (non-Finnish) · 27/1,147,342 alleles

Filtering AF 0.00161% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00138%

Overall 0.00175% 27/1,546,904 alleles · very rare exomes 26/1,395,142 · genomes 1/151,762 · 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.Val84=
Coding: c.252G>C
MANE Select: NM_032737
dbSNP: rs1972094753
Type: single nucleotide variant
Location: chr19:2456682 (GRCh38)
Gene constraint: LOEUF 0.399 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.82 · 2 PDB
Residue 84: the if rod domain; the 'linker 1' region

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 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-val84 (accessed [today's date]).

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