MAN2B2 p.Ser478=
c.1434G>A · VCV4689139
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 11.7%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.021 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -5.5 | GERP -2.6 |
| Overall | ||
| CADD | 0.336 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
11.7%
African / African-American · 8,795/75,030 alleles
Filtering AF
11.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 11.4%
Overall
0.651%
10,507/1,613,868 alleles · common
exomes 5,369/1,461,594 · genomes 5,138/152,274 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 11.7% | 9 |
| Middle Eastern | 1.34% | 75 |
| Remaining individualsnot grpmax-eligible | 0.982% | 102 |
| Admixed American | 0.871% | 115 |
| European (non-Finnish) | 0.0389% | 2,571 |
| South Asian | 0.0384% | 2,602 |
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.Ser478=
- Coding
- c.1434G>A
- MANE Select
- NM_015274
- Type
- single nucleotide variant
- Location
- chr4:6600651 (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-ser478 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown