SEMA6B p.Pro699=
c.2097C>T · VCV4940020
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0273%, mid)
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 -0.16 | GERP -1.6, phastCons 0.22 |
| Overall | ||
| CADD | 2.409 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0273%
Middle Eastern · 1/3,662 alleles
Filtering AF
0.000586%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000428%
Overall
0.00111%
14/1,266,648 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0273% | 3,662 |
| Admixed American | 0.00426% | 23,470 |
| Remaining individualsnot grpmax-eligible | 0.00214% | 46,696 |
| European (non-Finnish) | 0.00109% | 91,625 |
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.Pro699=
- Coding
- c.2097C>T
- MANE Select
- NM_032108
- Type
- single nucleotide variant
- Location
- chr19:4544171 (GRCh38)
- Gene constraint
- LOEUF 0.825 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.81
- Residue 699
- the 'disordered' region
Similar variants
- SEMA6B p.Pro699Leu Uncertain significance ★ ⚠ same residue
- SEMA6B p.Pro699Ser 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
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-pro699 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown