FLG p.Ser593fs
c.1776del · VCV3900622
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
ichthyosis vulgaris
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (3 of 3) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -10 | GERP -1.4 |
| Region caveats | ||
| Repeat context | tandem | chr1:152303355 segmental duplication, simple repeat · ambiguous alignment · reads may not map uniquely · confidence, not pathogenicity |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- FLG
- Protein
- p.Ser593fs
- Coding
- c.1776del
- MANE Select
- NM_002016
- Type
- Deletion
- Location
- chr1:152313110 (GRCh38)
- Gene constraint
- LOEUF 1.932 · pLI <0.01 (gnomAD)
- Residue 593
- the 'disordered' region
Similar variants
- FLG p.Arg612fs Pathogenic ★★ same condition
- FLG p.Ser2279fs Pathogenic/Likely pathogenic ★★ same condition
- FLG p.Arg1684fs Likely pathogenic ★ same condition
- FLG p.Gln2962fs Likely pathogenic ★ same condition
- FLG p.Gln776fs Likely pathogenic ★ same condition
- FLG p.Gly2876fs Likely pathogenic ★ same condition
- FLG p.Gly3683fs Likely pathogenic ★ same condition
- FLG p.Ile3642fs 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/flg-p-ser593fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown