MAN2B2 p.Pro555=
c.1665G>A · rs61745007 · VCV2654625
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.742%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.094 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.7 | GERP -1.8 |
| Overall | ||
| CADD | 2.016 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.742%
Middle Eastern · 45/6,062 alleles
Filtering AF
0.57%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.509%
Overall
0.0466%
753/1,614,190 alleles · rare
exomes 682/1,461,840 · genomes 71/152,350 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.742% | 135 |
| Ashkenazi Jewishnot grpmax-eligible | 0.568% | 176 |
| Remaining individualsnot grpmax-eligible | 0.109% | 919 |
| Admixed American | 0.09% | 1,112 |
| South Asian | 0.0867% | 1,153 |
| African / African-American | 0.0346% | 2,887 |
| European (non-Finnish) | 0.0259% | 3,856 |
| Finnishnot grpmax-eligible | 0.0109% | 9,147 |
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.Pro555=
- Coding
- c.1665G>A
- MANE Select
- NM_015274
- dbSNP
- rs61745007
- Type
- single nucleotide variant
- Location
- chr4:6605180 (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-pro555 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown