LMNA p.Pro508=
c.1524C>A · rs772978446 · VCV3074679
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Conditions
2
dilated cardiomyopathy
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 -0.028 | GERP -5, phastCons 0.74 |
| Overall | ||
| CADD | 6.426 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,060 alleles
Overall
0.000124%
2/1,613,292 alleles · ultra-rare
exomes 2/1,460,988 · genomes 0/152,304 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,060 |
| East Asian | 0.00223% | 44,846 |
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.Pro508=
- Coding
- c.1524C>A
- MANE Select
- NM_170707
- dbSNP
- rs772978446
- Type
- single nucleotide variant
- Location
- chr1:156137148 (GRCh38)
- Gene constraint
- LOEUF 0.412 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.55 · 28 PDB
- Residue 508
- the 'tail' region; a turn; the ltd domain
Similar variants
- LMNA p.Pro508Leu Uncertain significance ★★ ⚠ same residue
- LMNA p.Pro508His 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-pro508 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown