SEMA6B p.Pro557=
c.1671G>A · VCV4940022
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00539%, afr)
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 -20 | GERP -3.2 |
| Overall | ||
| CADD | 0.007 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00539%
African / African-American · 4/74,146 alleles
Filtering AF
0.00176%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00105%
Overall
0.00126%
20/1,583,704 alleles · very rare
exomes 18/1,431,602 · genomes 2/152,102 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00539% | 18,537 |
| East Asian | 0.00464% | 21,549 |
| South Asian | 0.00344% | 29,049 |
| Finnishnot grpmax-eligible | 0.00162% | 61,816 |
| European (non-Finnish) | 0.000859% | 116,431 |
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.Pro557=
- Coding
- c.1671G>A
- MANE Select
- NM_032108
- Type
- single nucleotide variant
- Location
- chr19:4546400 (GRCh38)
- Gene constraint
- LOEUF 0.825 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.81
Similar variants
- SEMA6B p.Pro557Leu Uncertain significance ★ ⚠ same residue
- SEMA6B p.Pro557Arg Likely benign ★ 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-pro557 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown