Is LMNB2 p.Arg231Trp (c.691C>T) pathogenic?

LMNB2 p.Arg231Trp (c.691C>T) is classified Uncertain significance in LMNB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-26). AlphaMissense: likely benign (0.148); Ultra-rare (popmax 0.0167%, amr); Associated with lipodystrophy, partial, acquired, susceptibility to.

How common is LMNB2 p.Arg231Trp (c.691C>T) in the general population?

LMNB2 p.Arg231Trp (c.691C>T) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

What do computational predictors say about LMNB2 p.Arg231Trp (c.691C>T)?

AlphaMissense predicts likely benign (score 0.148) — an in-silico prediction, not a clinical call.

LMNB2 p.Arg231Trp

Q: What condition is associated with LMNB2 p.Arg231Trp (c.691C>T)?

LMNB2 p.Arg231Trp (c.691C>T) is associated with lipodystrophy, partial, acquired, susceptibility to, progressive myoclonic epilepsy type 9 (ClinVar).

c.691C>T · rs760267703 · VCV542432

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.148 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

lipodystrophy, partial, acquired, susceptibility to

Computational evidence

Protein change
AlphaMissense	0.148	likely benign
REVEL	0.765	pathogenic-leaning
SaProt	LLR -13.08	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	Δ0.25	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 9.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 7,487 bp · p 0.38 · regional, not allelic
Overall
CADD	34.0	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 0.0167% Admixed American · 10/59,950 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00682%

Overall 0.000999% 16/1,601,600 alleles · ultra-rare exomes 14/1,449,402 · genomes 2/152,198 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	5,995
South Asian	0.0022%	45,518
European (non-Finnish)	0.000339%	294,883

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.Arg231Trp
Coding: c.691C>T
MANE Select: NM_032737
dbSNP: rs760267703
Type: single nucleotide variant
Location: chr19:2435165 (GRCh38)
Gene constraint: LOEUF 0.399 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.82 · 2 PDB
Residue 231: the if rod domain; the 'linker 2' 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 p.Arg231Gln Uncertain significance ★ ⚠ same residue
LMNB2 p.Arg231Gly 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

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-arg231trp (accessed [today's date]).

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