MTTP p.Thr123=
c.369G>A · rs562221537 · VCV1090457
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0159%, 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 0.96 | GERP 0.91, phastCons 1 |
| Overall | ||
| CADD | 9.312 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0159%
European (non-Finnish) · 188/1,179,798 alleles
Filtering AF
0.014%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0133%
Overall
0.0125%
202/1,613,542 alleles · ultra-rare
exomes 194/1,461,370 · genomes 8/152,172 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0159% | 6,276 |
| African / African-American | 0.00667% | 15,000 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,622 |
| South Asian | 0.00439% | 22,766 |
| East Asian | 0.00223% | 44,836 |
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.Thr123=
- Coding
- c.369G>A
- MANE Select
- NM_001386140
- dbSNP
- rs562221537
- Type
- single nucleotide variant
- Location
- chr4:99583493 (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 123
- the vitellogenin domain; a β-strand
Similar variants
- MTTP p.Thr123Met Uncertain significance ★★ ⚠ same residue
- MTTP p.Thr123Ala 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
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-thr123 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown