Is LMNB2 p.Ser614= (c.1842A>G) pathogenic?

LMNB2 p.Ser614= (c.1842A>G) is classified Likely benign in LMNB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-15). Very rare (popmax 0.00267%, afr); Associated with lipodystrophy, partial, acquired, susceptibility to.

How common is LMNB2 p.Ser614= (c.1842A>G) in the general population?

LMNB2 p.Ser614= (c.1842A>G) is very rare (popmax 0.00267%, afr) (gnomAD).

LMNB2 p.Ser614=

Q: What condition is associated with LMNB2 p.Ser614= (c.1842A>G)?

LMNB2 p.Ser614= (c.1842A>G) is associated with lipodystrophy, partial, acquired, susceptibility to, progressive myoclonic epilepsy type 9 (ClinVar).

c.1842A>G · rs1249699732 · VCV749456

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -13	GERP -2.3
Overall
CADD	0.069	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,830 alleles

Filtering AF 0.000444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,610,128 alleles · very rare exomes 2/1,457,940 · genomes 1/152,188 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,415
Admixed American	0.00167%	59,996

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.Ser614=
Coding: c.1842A>G
MANE Select: NM_032737
dbSNP: rs1249699732
Type: single nucleotide variant
Location: chr19:2430932 (GRCh38)
Gene constraint: LOEUF 0.399 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.82 · 2 PDB
Residue 614: the 'tail' region; the 'disordered' 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-ser614 (accessed [today's date]).

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