Is LMNB2 p.Arg73Pro (c.218G>C) pathogenic?

LMNB2 p.Arg73Pro (c.218G>C) is classified Uncertain significance in LMNB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-18). AlphaMissense: likely pathogenic (0.965); Very rare (popmax 0.00026%, nfe).

How common is LMNB2 p.Arg73Pro (c.218G>C) in the general population?

LMNB2 p.Arg73Pro (c.218G>C) is very rare (popmax 0.00026%, nfe) (gnomAD).

What do computational predictors say about LMNB2 p.Arg73Pro (c.218G>C)?

AlphaMissense predicts likely pathogenic (score 0.965) — an in-silico prediction, not a clinical call.

LMNB2 p.Arg73Pro

c.218G>C · rs1327659677 · VCV2327587

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.965 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00026%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.965	likely pathogenic · top 5% in LMNB2
REVEL	0.392	indeterminate
SaProt	LLR -14.41	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP 0.8, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 18 kb · p 2.9e-08 · regional, not allelic
Overall
CADD	21.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00026% European (non-Finnish) · 3/1,155,854 alleles

Filtering AF 6.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000192% 3/1,564,378 alleles · very rare exomes 1/1,412,656 · genomes 2/151,722 · 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.Arg73Pro
Coding: c.218G>C
MANE Select: NM_032737
dbSNP: rs1327659677
Type: single nucleotide variant
Location: chr19:2456716 (GRCh38)
Gene constraint: LOEUF 0.399 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.82 · 2 PDB
Residue 73: the if rod domain; the 'coil 1a' region

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

Similar variants

LMNB2 p.Glu398Lys Pathogenic ★★ same type
LMNB2 c.1202+5G>A Uncertain significance ★★ same type
LMNB2 p.Ala178Thr Uncertain significance ★★ ⚠ same type
LMNB2 p.Ala299Val Uncertain significance ★★ ⚠ same type
LMNB2 p.Ala29Pro Uncertain significance ★★ ⚠ same type
LMNB2 p.Ala567Thr Uncertain significance ★★ ⚠ same type
LMNB2 p.Arg104Gly Uncertain significance ★★ ⚠ same type
LMNB2 p.Arg114His 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-arg73pro (accessed [today's date]).

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