Is LMNB2 p.Val577= (c.1731G>A) pathogenic?

LMNB2 p.Val577= (c.1731G>A) is classified Likely benign in LMNB2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-05-26). Very rare (popmax 0.0011%, sas); Associated with LMNB2-related disorder.

What condition is associated with LMNB2 p.Val577= (c.1731G>A)?

LMNB2 p.Val577= (c.1731G>A) is associated with LMNB2-related disorder (ClinVar).

How common is LMNB2 p.Val577= (c.1731G>A) in the general population?

LMNB2 p.Val577= (c.1731G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

LMNB2 p.Val577=

c.1731G>A · rs2512232304 · VCV3056931

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

LMNB2-related disorder

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 1.3	GERP 0.33, phastCons 1
Overall
CADD	5.571	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,088 alleles

Overall 6.2e-05% 1/1,614,172 alleles · very rare exomes 1/1,461,836 · genomes 0/152,336 · 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.Val577=
Coding: c.1731G>A
MANE Select: NM_032737
dbSNP: rs2512232304
Type: single nucleotide variant
Location: chr19:2431638 (GRCh38)
Gene constraint: LOEUF 0.399 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.82 · 2 PDB
Residue 577: the 'tail' region; the ltd domain; a β-strand

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

Disease context

LMNB2-related disorder

Similar variants

LMNB2 p.Val577Met Uncertain significance ★ ⚠ same residue
LMNB2 p.Glu398Lys Pathogenic ★★ same condition
LMNB2 p.Ser247Arg Uncertain significance ★★ ⚠ same condition
LMNB2 p.Gly550Arg Uncertain significance ★ ⚠ same condition
LMNB2 c.1203-7C>G Likely benign same condition
LMNB2 c.*2C>A Likely benign same condition
LMNB2 c.*9_*21del Likely benign same condition
LMNB2 c.1202+5G>A Uncertain significance ★★ same type

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-val577 (accessed [today's date]).

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