Is LMNA p.Asp552= (c.1656C>T) pathogenic?

LMNA p.Asp552= (c.1656C>T) is classified Conflicting classifications of pathogenicity in LMNA (ClinVar, Conflicting submitters, 15 submitters; last evaluated 2026-01-09). Ultra-rare (popmax 0.0108%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with LMNA p.Asp552= (c.1656C>T)?

LMNA p.Asp552= (c.1656C>T) is associated with Cardiovascular phenotype, cardiomyopathy, dilated cardiomyopathy (ClinVar).

How common is LMNA p.Asp552= (c.1656C>T) in the general population?

LMNA p.Asp552= (c.1656C>T) is ultra-rare (popmax 0.0108%, nfe) (gnomAD).

LMNA p.Asp552=

c.1656C>T · rs370219874 · VCV48047

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 15 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0108%, nfe)

Conditions

Cardiovascular phenotype

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 -5.7	GERP -4.5
Overall
CADD	12.76	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0108% European (non-Finnish) · 124/1,149,362 alleles

Filtering AF 0.00915% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00864%

Overall 0.00938% 146/1,555,920 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0108%	9,269
South Asian	0.00949%	10,536
Remaining individualsnot grpmax-eligible	0.00829%	12,062
African / African-American	0.00815%	12,265
Admixed American	0.00391%	25,573
Ashkenazi Jewishnot grpmax-eligible	0.00349%	28,656

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: LMNA
Protein: p.Asp552=
Coding: c.1656C>T
MANE Select: NM_170707
dbSNP: rs370219874
Type: single nucleotide variant
Location: chr1:156137701 (GRCh38)
Gene constraint: LOEUF 0.412 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.55 · 28 PDB
Residue 552: the 'tail' region; the 'disordered' region

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

Disease context

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

Also linked: cardiomyopathy dilated cardiomyopathy Charcot-Marie-Tooth disease type 2

Similar variants

LMNA p.Asp552Ala Uncertain significance ★★ ⚠ same residue
LMNA p.Asp552Asn Uncertain significance ★★ ⚠ same residue
LMNA c.1157+1G>A Pathogenic/Likely pathogenic ★★ same condition
LMNA c.1157+1G>T Pathogenic/Likely pathogenic ★★ same condition
LMNA c.1157+2T>A Pathogenic ★★ same condition
LMNA c.1380+1G>A Pathogenic ★★ same condition
LMNA c.1489-2A>G Likely pathogenic ★★ same condition
LMNA c.1608+1G>A 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-asp552 (accessed [today's date]).

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