SRCAP p.Leu2558fs
c.7670dup · VCV4929431
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
SRCAP-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (34 of 34) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 0.72 | GERP -2.2, phastCons 0.54 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- SRCAP
- Protein
- p.Leu2558fs
- Coding
- c.7670dup
- MANE Select
- NM_006662
- Type
- Duplication
- Location
- chr16:30737709 (GRCh38)
- Gene constraint
- LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 2558
- a UniProt-annotated variant site (in dehmba); a UniProt-annotated variant site (in flhs)
Disease context
SRCAP-related disorder
Similar variants
- SRCAP p.Arg1007fs Pathogenic ★ same condition
- SRCAP p.Leu2558= Likely benign ★ same residue
- SRCAP p.Arg2435Ter Pathogenic/Likely pathogenic ★★ same condition
- SRCAP p.Arg2444Ter Pathogenic ★★ same condition
- SRCAP p.Arg2748Ter Pathogenic ★★ same condition
- SRCAP p.Gln3043His Uncertain significance ★★ ⚠ same condition
- SRCAP p.Gln3202His Uncertain significance ★★ same condition
- SRCAP p.Leu2652Arg Uncertain significance ★★ 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/srcap-p-leu2558fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown