MAN2B2 p.Arg777=
c.2331G>C · VCV4689027
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.14%, afr)
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 -0.047 | GERP -1.2, phastCons 0.1 |
| Overall | ||
| CADD | 4.017 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.14%
African / African-American · 854/75,048 alleles
Filtering AF
1.07%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.05%
Overall
0.0616%
994/1,614,208 alleles · low-frequency
exomes 503/1,461,874 · genomes 491/152,334 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.14% | 88 |
| Remaining individualsnot grpmax-eligible | 0.0992% | 1,008 |
| Admixed American | 0.0966% | 1,035 |
| Middle Eastern | 0.033% | 3,030 |
| South Asian | 0.00549% | 18,218 |
| European (non-Finnish) | 0.0011% | 90,771 |
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.Arg777=
- Coding
- c.2331G>C
- MANE Select
- NM_015274
- Type
- single nucleotide variant
- Location
- chr4:6610951 (GRCh38)
- Gene constraint
- LOEUF 1.023 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.55
Similar variants
- MAN2B2 p.Arg777Gln Likely benign ★ same residue
- 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
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-arg777 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown