LMNA p.Ser573=
c.1719G>A · rs759853354 · VCV1107745
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.0066%, sas)
Conditions
2
Charcot-Marie-Tooth disease type 2
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 3.2 | GERP 2.2, phastCons 1 |
| Overall | ||
| CADD | 14.17 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0066%
South Asian · 6/90,958 alleles
Filtering AF
0.00287%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00195%
Overall
0.00089%
13/1,460,064 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0066% | 15,160 |
| European (non-Finnish) | 0.000593% | 168,542 |
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.Ser573=
- Coding
- c.1719G>A
- MANE Select
- NM_170707
- dbSNP
- rs759853354
- Type
- single nucleotide variant
- Location
- chr1:156138508 (GRCh38)
- Gene constraint
- LOEUF 0.412 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.55 · 28 PDB
- Residue 573
- the 'tail' region; the 'disordered' region; a UniProt-annotated variant site (in cmd1a, fpld2 and mada)
Similar variants
- LMNA p.Ser573Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- LMNA p.Ter573= Likely benign ★ same residue
- LMNA c.1157+1G>A Pathogenic/Likely pathogenic ★★ same condition
- LMNA c.1157+1G>T Pathogenic/Likely 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
- LMNA c.1608+2T>G 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-ser573 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown