MTTP p.Leu435=
c.1305T>C · rs1725702372 · VCV1126389
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
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 -6.3 | GERP -3.5 |
| Overall | ||
| CADD | 0.492 | 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
- MTTP
- Protein
- p.Leu435=
- Coding
- c.1305T>C
- MANE Select
- NM_001386140
- dbSNP
- rs1725702372
- Type
- single nucleotide variant
- Location
- chr4:99601675 (GRCh38)
- Gene constraint
- LOEUF 0.672 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 86.73 · 2 PDB
- Residue 435
- a UniProt-annotated variant site (in abl; no loss on localization to the endoplasmic reticulum; inhibits triglyceride transfer activity); the vitellogenin domain; an α-helix
Similar variants
- MTTP p.Leu435fs Pathogenic ★ same residue
- MTTP c.1067+1G>C Likely pathogenic ★★ same type
- MTTP c.1236+1G>A Pathogenic/Likely pathogenic ★★ same type
- MTTP c.1769+2T>C Pathogenic/Likely pathogenic ★★ same type
- MTTP c.1867+1G>A Pathogenic ★★ same type
- MTTP c.1867+5G>A Pathogenic/Likely pathogenic ★★ same type
- MTTP c.1868-2A>G Likely pathogenic ★★ same type
- MTTP c.2342+1G>A 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/mttp-p-leu435 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown