MTTP p.Asp169=
c.507T>C · rs1388191865 · VCV2804178
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00268%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>G here scores Δ0.37 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.008 | GERP -2.2, phastCons 0.87 |
| Overall | ||
| CADD | 8.038 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00268%
African / African-American · 2/74,640 alleles
Filtering AF
0.000445%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.000187%
3/1,605,420 alleles · very rare
exomes 2/1,453,238 · genomes 1/152,182 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00268% | 37,320 |
| European (non-Finnish) | 8.53e-05% | 1,172,374 |
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
- MTTP
- Protein
- p.Asp169=
- Coding
- c.507T>C
- MANE Select
- NM_001386140
- dbSNP
- rs1388191865
- Type
- single nucleotide variant
- Location
- chr4:99591240 (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 169
- a UniProt-annotated variant site (in abl; no loss on localization to the endoplasmic reticulum; does not reduce interaction with apob; inhibits interaction with p4hb/pdi; inhibits phospholipid or triglyceride transfer activity; inhibits apolipoprotein b secretion); the vitellogenin domain; a β-strand
Similar variants
- MTTP p.Asp169Val Likely 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-asp169 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown