MAN2B2 p.Pro392=
c.1176G>A · VCV4688948
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0135%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.092 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -6.8 | GERP -2.8 |
| Overall | ||
| CADD | 0.349 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0135%
Admixed American · 8/59,156 alleles
Filtering AF
0.0067%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00488%
Overall
0.00237%
38/1,605,500 alleles · ultra-rare
exomes 30/1,453,332 · genomes 8/152,168 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0135% | 7,394 |
| African / African-American | 0.0107% | 9,325 |
| Remaining individualsnot grpmax-eligible | 0.00483% | 20,703 |
| European (non-Finnish) | 0.00162% | 61,870 |
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
- MAN2B2
- Protein
- p.Pro392=
- Coding
- c.1176G>A
- MANE Select
- NM_015274
- Type
- single nucleotide variant
- Location
- chr4:6597231 (GRCh38)
- Gene constraint
- LOEUF 1.023 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.55
Similar variants
- MAN2B2 p.Gln615Ter Pathogenic/Likely pathogenic ★★ same type
- MAN2B2 p.Trp284Ter Pathogenic/Likely pathogenic ★★ same type
- MAN2B2 p.Ala155Thr Uncertain significance ★★ ⚠ same type
- MAN2B2 p.Ala868Thr Uncertain significance ★★ ⚠ same type
- MAN2B2 p.Arg411His Uncertain significance ★★ ⚠ same type
- MAN2B2 p.Arg447Gly Uncertain significance ★★ ⚠ same type
- MAN2B2 p.Arg683Gln Uncertain significance ★★ ⚠ same type
- MAN2B2 p.Arg975Ser Uncertain significance ★★ ⚠ 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/man2b2-p-pro392 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown