Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 9 submitters
gnomAD v4.1
Common
common (popmax 25.1%, afr) — too common for a highly-penetrant pathogenic allele
Conditions
1
abetalipoproteinemia
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.021 | GERP -2, phastCons 0.95 |
| Overall | ||
| CADD | 9.685 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
25.1%
African / African-American · 18,797/74,826 alleles
Filtering AF
24.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 24.7%
Overall
8.08%
130,223/1,611,970 alleles · common
exomes 111,762/1,459,780 · genomes 18,461/152,190 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 25.1% | 4 |
| East Asian | 21.1% | 5 |
| South Asian | 11.1% | 9 |
| Remaining individualsnot grpmax-eligible | 8.9% | 11 |
| Middle Eastern | 8.58% | 12 |
| Admixed American | 7.45% | 13 |
| European (non-Finnish) | 6.5% | 15 |
| Ashkenazi Jewishnot grpmax-eligible | 5.71% | 17 |
| Amishnot grpmax-eligible | 4.61% | 22 |
| Finnishnot grpmax-eligible | 4.58% | 22 |
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.Cys174=
- Coding
- c.522T>C
- MANE Select
- NM_001386140
- dbSNP
- rs982424
- Type
- single nucleotide variant
- Location
- chr4:99591255 (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 174
- the vitellogenin domain; a disulfide bond; a β-strand
Disease context
abetalipoproteinemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Abetalipoproteinemia (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Childhood, Infancy
- Prevalence
- <1 / 1 000 000 (Worldwide)
Similar variants
- MTTP c.1067+1G>C Likely pathogenic ★★ same condition
- MTTP c.1769+2T>C Pathogenic/Likely pathogenic ★★ same condition
- MTTP c.1867+1G>A Pathogenic ★★ same condition
- MTTP c.1867+5G>A Pathogenic/Likely pathogenic ★★ same condition
- MTTP c.1868-2A>G Likely pathogenic ★★ same condition
- MTTP c.2342+1G>A Pathogenic ★★ same condition
- MTTP c.502-1G>C Likely pathogenic ★★ same condition
- MTTP c.502-2A>G Likely pathogenic ★★ same condition
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-cys174 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown