PDE5A p.His670=
c.2010T>C · rs199578826 · VCV2655054
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.133%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.242 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.2 | GERP -1.1, phastCons 1 |
| Overall | ||
| CADD | 7.612 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.133%
Middle Eastern · 8/6,034 alleles
Filtering AF
0.0659%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0481%
Overall
0.0152%
244/1,606,040 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.133% | 754 |
| Admixed American | 0.0567% | 1,763 |
| Remaining individualsnot grpmax-eligible | 0.0402% | 2,487 |
| South Asian | 0.0155% | 6,468 |
| European (non-Finnish) | 0.0136% | 7,334 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00679% | 14,721 |
| African / African-American | 0.00134% | 74,830 |
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
- PDE5A
- Protein
- p.His670=
- Coding
- c.2010T>C
- MANE Select
- NM_001083
- dbSNP
- rs199578826
- Type
- single nucleotide variant
- Location
- chr4:119511125 (GRCh38)
- Gene constraint
- LOEUF 0.704 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.32 · 50 PDB
- Residue 670
- the pdease domain
Similar variants
- PDE5A c.2190-4G>A Benign/Likely benign ★★ same type
- PDE5A p.Arg740Lys Likely benign ★★ same type
- PDE5A p.Glu119Val Benign/Likely benign ★★ same type
- PDE5A p.Glu475= Benign/Likely benign ★★ same type
- PDE5A p.Glu808= Benign ★★ same type
- PDE5A p.Lys480Gln Benign ★★ same type
- PDE5A p.Pro671= Benign ★★ same type
- PDE5A p.Ala235Val 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/pde5a-p-his670 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown