PDE6B p.His557=
c.1671C>T · rs919002816 · VCV1642684
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00182%, amr)
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 1.6 | GERP 0.16, phastCons 1 |
| Overall | ||
| CADD | 8.768 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00182%
Admixed American · 1/54,916 alleles
Overall
0.000657%
1/152,214 alleles · very rare
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
- PDE6B
- Protein
- p.His557=
- Coding
- c.1671C>T
- MANE Select
- NM_000283
- dbSNP
- rs919002816
- Type
- single nucleotide variant
- Location
- chr4:662190 (GRCh38)
- Gene constraint
- LOEUF 1.238 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.72
- Residue 557
- a binding site; a UniProt-annotated variant site (in rp40; autosomal dominant); the pdease domain; an active site
Similar variants
- PDE6B p.His557Arg Likely pathogenic ★★ same residue
- PDE6B p.His557Tyr Pathogenic ★★ same residue
- PDE6B c.1059+2T>G Likely pathogenic ★★ same type
- PDE6B c.1060-1G>T Pathogenic/Likely pathogenic ★★ same type
- PDE6B c.1107+1G>T Likely pathogenic ★★ same type
- PDE6B c.1107+3A>G Pathogenic/Likely pathogenic ★★ same type
- PDE6B c.1468-2A>G Pathogenic/Likely pathogenic ★★ same type
- PDE6B c.1832+1G>T Pathogenic ★★ 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/pde6b-p-his557 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown