MAN2B2 p.Ala560=
c.1680G>A · VCV4689113
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 2.94%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.004 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -1.7 | GERP -1.2 |
| Overall | ||
| CADD | 6.367 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.94%
African / African-American · 2,203/75,050 alleles
Filtering AF
2.83%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.79%
Overall
0.18%
2,913/1,614,190 alleles · low-frequency
exomes 1,646/1,461,860 · genomes 1,267/152,330 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.94% | 34 |
| Middle Eastern | 0.247% | 404 |
| Remaining individualsnot grpmax-eligible | 0.237% | 422 |
| Admixed American | 0.227% | 441 |
| European (non-Finnish) | 0.0325% | 3,073 |
| Finnishnot grpmax-eligible | 0.0187% | 5,335 |
| South Asian | 0.0143% | 7,006 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,604 |
| East Asian | 0.00223% | 44,890 |
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.Ala560=
- Coding
- c.1680G>A
- MANE Select
- NM_015274
- Type
- single nucleotide variant
- Location
- chr4:6605195 (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-ala560 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown