LMAN2 p.Phe253=
c.759C>T · VCV4546791
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00878%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.2 | GERP -4.8 |
| Overall | ||
| CADD | 1.1 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00878%
South Asian · 8/91,088 alleles
Filtering AF
0.00437%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00312%
Overall
0.00279%
45/1,613,770 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00878% | 11,386 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,625 |
| African / African-American | 0.00266% | 37,534 |
| European (non-Finnish) | 0.00254% | 39,331 |
| East Asian | 0.00223% | 44,880 |
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
- LMAN2
- Protein
- p.Phe253=
- Coding
- c.759C>T
- MANE Select
- NM_006816
- Type
- single nucleotide variant
- Location
- chr5:177337167 (GRCh38)
- Gene constraint
- LOEUF 0.752 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.45
- Residue 253
- the l-type lectin-like domain
Similar variants
- LMAN2 p.Ala134Thr Uncertain significance ★ ⚠ same type
- LMAN2 p.Ala200Val Uncertain significance ★ same type
- LMAN2 p.Ala44Ser Uncertain significance ★ ⚠ same type
- LMAN2 p.Arg139Gln Uncertain significance ★ ⚠ same type
- LMAN2 p.Arg139Trp Uncertain significance ★ ⚠ same type
- LMAN2 p.Arg141Cys Uncertain significance ★ same type
- LMAN2 p.Arg172His Uncertain significance ★ ⚠ same type
- LMAN2 p.Arg195Cys 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/lman2-p-phe253 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown