PDE5A p.His274=
c.822T>C · rs144600278 · VCV750553
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.25%, sas)
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 -1.7 | GERP -4.2 |
| Overall | ||
| CADD | 3.555 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.25%
South Asian · 211/84,484 alleles
Filtering AF
0.222%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.211%
Overall
0.0383%
606/1,580,684 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.25% | 400 |
| Middle Eastern | 0.0335% | 2,983 |
| European (non-Finnish) | 0.0323% | 3,096 |
| Remaining individualsnot grpmax-eligible | 0.0114% | 8,737 |
| Admixed American | 0.0106% | 9,451 |
| African / African-American | 0.00675% | 14,816 |
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.His274=
- Coding
- c.822T>C
- MANE Select
- NM_001083
- dbSNP
- rs144600278
- Type
- single nucleotide variant
- Location
- chr4:119596532 (GRCh38)
- Gene constraint
- LOEUF 0.704 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.32 · 50 PDB
- Residue 274
- the gaf 1 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-his274 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown