PLEC p.Ala1583=
c.4749C>T · rs1554701088 · VCV752925
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000171%, nfe)
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 -0.66 | |
| Overall | ||
| CADD | 1.145 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000171%
European (non-Finnish) · 2/1,168,110 alleles
Filtering AF
2.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000127%
2/1,573,496 alleles · very rare
exomes 2/1,421,272 · genomes 0/152,224 · joint denominator
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
- PLEC
- Protein
- p.Ala1583=
- Coding
- c.4749C>T
- MANE Select
- NM_201384
- dbSNP
- rs1554701088
- Type
- single nucleotide variant
- Location
- chr8:143925180 (GRCh38)
- Gene constraint
- LOEUF 0.726 · pLI <0.01 (gnomAD)
- Residue 1583
- the 'required for interaction with intermediate filament proteins' region; the 'central fibrous rod domain' region
Similar variants
- PLEC p.Ala1583Thr Uncertain significance ★ ⚠ same residue
- PLEC p.Ala1583Val Uncertain significance ★ ⚠ same residue
- PLEC p.Arg1490Ter Pathogenic/Likely pathogenic ★★ same type
- PLEC p.Arg1973Trp Pathogenic ★★ ⚠ same type
- PLEC p.Arg2027Ter Pathogenic ★★ same type
- PLEC p.Arg2292Ter Pathogenic ★★ same type
- PLEC p.Arg2324Ter Pathogenic ★★ same type
- PLEC p.Arg2394Ter Pathogenic ★★ same type
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/plec-p-ala1583 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown