SEMA6B p.Pro11=
c.33G>C · VCV4940034
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.225%, eas)
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 1 | GERP 0.44, phastCons 0.49 |
| Overall | ||
| CADD | 13.05 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.225%
East Asian · 57/25,302 alleles
Filtering AF
0.178%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.162%
Overall
0.0828%
841/1,015,514 alleles · rare
exomes 831/866,862 · genomes 10/148,652 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.225% | 444 |
| Ashkenazi Jewishnot grpmax-eligible | 0.131% | 764 |
| Middle Eastern | 0.11% | 913 |
| Remaining individualsnot grpmax-eligible | 0.105% | 951 |
| European (non-Finnish) | 0.0846% | 1,182 |
| South Asian | 0.0591% | 1,693 |
| Admixed American | 0.0407% | 2,456 |
| African / African-American | 0.0336% | 2,972 |
| Finnishnot grpmax-eligible | 0.0248% | 4,028 |
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
- SEMA6B
- Protein
- p.Pro11=
- Coding
- c.33G>C
- MANE Select
- NM_032108
- Type
- single nucleotide variant
- Location
- chr19:4558425 (GRCh38)
- Gene constraint
- LOEUF 0.825 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.81
Similar variants
- SEMA6B p.Pro11Leu Uncertain significance ★ ⚠ same residue
- SEMA6B p.Gln660Ter Pathogenic/Likely pathogenic ★★ same type
- SEMA6B p.Thr713Met Likely pathogenic ★★ ⚠ same type
- SEMA6B p.Gly538Ser Uncertain significance ★★ ⚠ same type
- SEMA6B p.Gly852Asp Uncertain significance ★★ ⚠ same type
- SEMA6B p.His180Asp Uncertain significance ★★ ⚠ same type
- SEMA6B p.Ser500Asn Uncertain significance ★★ ⚠ same type
- SEMA6B p.Ser851Cys 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/sema6b-p-pro11 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown