MTTP p.Ala263=
c.789A>G · rs765252900 · VCV1122487
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00466%, nfe)
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 -0.62 | GERP 0.56 |
| Overall | ||
| CADD | 2.454 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00466%
European (non-Finnish) · 55/1,179,928 alleles
Filtering AF
0.00367%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00329%
Overall
0.00353%
57/1,613,970 alleles · very rare
exomes 55/1,461,740 · genomes 2/152,230 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00466% | 21,453 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
| African / African-American | 0.00133% | 74,932 |
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.Ala263=
- Coding
- c.789A>G
- MANE Select
- NM_001386140
- dbSNP
- rs765252900
- Type
- single nucleotide variant
- Location
- chr4:99594763 (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 263
- the vitellogenin domain
Similar variants
- MTTP p.Ala263Thr Uncertain significance ★ ⚠ 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-ala263 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown