MTTP p.Ala229=
c.687T>C · rs1177104199 · VCV798425
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
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 -0.83 | GERP -2.3, phastCons 0.013 |
| Overall | ||
| CADD | 9.193 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/59,968 alleles
Filtering AF
0.000247%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000159%
Overall
0.000548%
8/1,460,748 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 59,968 |
| European (non-Finnish) | 0.000594% | 168,462 |
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.Ala229=
- Coding
- c.687T>C
- MANE Select
- NM_001386140
- dbSNP
- rs1177104199
- Type
- single nucleotide variant
- Location
- chr4:99591719 (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 229
- the vitellogenin domain; a β-strand
Similar variants
- MTTP p.Ala229Gly 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-ala229 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown