KLHL40 p.Arg231=
c.693C>T · rs2125844758 · VCV1551592
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
nemaline myopathy 8
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.5 | GERP -4.5 |
| Overall | ||
| CADD | 12.71 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- KLHL40
- Protein
- p.Arg231=
- Coding
- c.693C>T
- MANE Select
- NM_152393
- dbSNP
- rs2125844758
- Type
- single nucleotide variant
- Location
- chr3:42686311 (GRCh38)
- Gene constraint
- LOEUF 1.128 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.70 · 1 PDB
- Residue 231
- a UniProt-annotated variant site (in nem8); the back domain
Disease context
nemaline myopathy 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Severe congenital nemaline myopathy (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy, Neonatal
- Prevalence
- <1 / 1 000 000 (Europe)
Similar variants
- KLHL40 c.1608-1G>A Pathogenic ★★ same condition
- KLHL40 p.Arg500Cys Pathogenic/Likely pathogenic ★★ same condition
- KLHL40 p.Arg59Pro Likely pathogenic ★★ same condition
- KLHL40 p.Gln497Ter Pathogenic/Likely pathogenic ★★ same condition
- KLHL40 p.Glu235Ter Pathogenic/Likely pathogenic ★★ same condition
- KLHL40 p.Glu528Lys Pathogenic/Likely pathogenic ★★ same condition
- KLHL40 p.Thr506Pro Pathogenic ★★ same condition
- KLHL40 p.Trp201Ter 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/klhl40-p-arg231 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown