Is LMNA p.Arg439fs (c.1316_1322del) pathogenic?

LMNA p.Arg439fs (c.13161322del) is classified Pathogenic in LMNA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-14). No gnomAD frequency available for this variant; Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with LMNA p.Arg439fs (c.1316_1322del)?

LMNA p.Arg439fs (c.1316_1322del) is associated with Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is LMNA p.Arg439fs (c.1316_1322del) in the general population?

LMNA p.Arg439fs (c.1316_1322del) is no gnomAD frequency available for this variant (gnomAD).

LMNA p.Arg439fs

c.1316_1322del · rs2527999623 · VCV2112104

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Charcot-Marie-Tooth disease type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 7 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: LMNA
Protein: p.Arg439fs
Coding: c.1316_1322del
MANE Select: NM_170707
dbSNP: rs2527999623
Type: Deletion
Location: chr1:156136369 (GRCh38)
Gene constraint: LOEUF 0.412 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.55 · 28 PDB
Residue 439: the 'tail' region; the 'disordered' region; a UniProt-annotated variant site (in fpld2; increase in nuclear blebbing and formation of honeycomb-like structures in the nuclei with no accumulation of prelamin a in skin fibroblasts; causes oligomerization of the c-terminal globular domain of lamins a and c under no-reducing conditions and increases binding affinity for dna; increases sensitivity to oxidative stress; no significant differences in stability and structure compared with the wild-type); a β-strand; the ltd domain

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

Disease context

Charcot-Marie-Tooth disease type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LMNA p.Arg439= Likely benign ★★ same residue
LMNA p.Arg439Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
LMNA p.Arg439His Conflicting classifications of pathogenicity ★ ⚠ same residue
LMNA c.1142_1157+1del Pathogenic/Likely pathogenic ★★ same condition
LMNA p.Ala175fs Pathogenic ★★ same condition
LMNA p.Ala441fs Pathogenic ★★ same condition
LMNA p.Ala504fs Pathogenic/Likely pathogenic ★★ same condition
LMNA p.Arg275fs Pathogenic/Likely pathogenic ★★ 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/lmna-p-arg439fs (accessed [today's date]).

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