MAN1B1 p.Pro652=
c.1956T>C · rs75234317 · VCV365976
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.15%, afr)
Conditions
2
Inborn genetic diseases
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 0.19 | GERP -3.4, phastCons 0.27 |
| Overall | ||
| CADD | 9.33 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.15%
African / African-American · 862/75,022 alleles
Filtering AF
1.09%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.06%
Overall
0.0581%
938/1,613,894 alleles · low-frequency
exomes 476/1,461,638 · genomes 462/152,256 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.15% | 87 |
| Remaining individualsnot grpmax-eligible | 0.0768% | 1,302 |
| Admixed American | 0.0367% | 2,728 |
| Middle Eastern | 0.0165% | 6,062 |
| South Asian | 0.0011% | 91,080 |
| European (non-Finnish) | 0.000339% | 294,998 |
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
- MAN1B1
- Protein
- p.Pro652=
- Coding
- c.1956T>C
- MANE Select
- NM_016219
- dbSNP
- rs75234317
- Type
- single nucleotide variant
- Location
- chr9:137108447 (GRCh38)
- Gene constraint
- LOEUF 1.134 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.36 · 6 PDB
Similar variants
- MAN1B1 p.Pro652Leu Uncertain significance ★ ⚠ same residue
- MAN1B1 p.Arg334Cys Pathogenic/Likely pathogenic ★★ same condition
- MAN1B1 p.Gln162Ter Pathogenic ★★ same condition
- MAN1B1 p.Gly359Ter Pathogenic/Likely pathogenic ★★ same condition
- MAN1B1 c.*404T>C Uncertain significance ★★ same condition
- MAN1B1 p.Ala112Val Uncertain significance ★★ ⚠ same condition
- MAN1B1 p.Ala211Thr Uncertain significance ★★ ⚠ same condition
- MAN1B1 p.Ala226Val Uncertain significance ★★ ⚠ 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/man1b1-p-pro652 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown