Is LMNA p.Arg331fs (c.991_992del) pathogenic?

LMNA p.Arg331fs (c.991992del) is classified Pathogenic/Likely pathogenic in LMNA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2017-11-30). Absent from gnomAD; Associated with cardiomyopathy.

What condition is associated with LMNA p.Arg331fs (c.991_992del)?

LMNA p.Arg331fs (c.991_992del) is associated with cardiomyopathy, Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is LMNA p.Arg331fs (c.991_992del) in the general population?

LMNA p.Arg331fs (c.991_992del) is absent from gnomAD (gnomAD).

LMNA p.Arg331fs

c.991_992del · rs1553265647 · VCV543224

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

cardiomyopathy

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 6 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.5, 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.Arg331fs
Coding: c.991_992del
MANE Select: NM_170707
dbSNP: rs1553265647
Type: Deletion
Location: chr1:156135954 (GRCh38)
Gene constraint: LOEUF 0.412 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.55 · 28 PDB
Residue 331: the 'coil 2' region; the 'necessary and sufficient for the interaction with iffo1' region; an α-helix; the if rod domain

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

Disease context

cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease type 2

Similar variants

LMNA p.Arg331Pro Likely pathogenic ★★ same residue
LMNA p.Arg331Gly Likely pathogenic ★ same residue
LMNA p.Arg331Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
LMNA p.Arg331Trp 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

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-arg331fs (accessed [today's date]).

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