Is PDE5A p.Lys480Gln (c.1438A>C) pathogenic?

PDE5A p.Lys480Gln (c.1438A>C) is classified Benign in PDE5A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-02-08). AlphaMissense: likely benign (0.0828); Low-frequency (popmax 2.71%, afr).

How common is PDE5A p.Lys480Gln (c.1438A>C) in the general population?

PDE5A p.Lys480Gln (c.1438A>C) is low-frequency (popmax 2.71%, afr) (gnomAD).

What do computational predictors say about PDE5A p.Lys480Gln (c.1438A>C)?

AlphaMissense predicts likely benign (score 0.0828) — an in-silico prediction, not a clinical call.

PDE5A p.Lys480Gln

c.1438A>C · rs114790192 · VCV724466

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0828 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.71%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0828	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -5.22	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.91	GERP -2.3, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 130 kb · p 1.5e-08 · regional, not allelic
Overall
CADD	16.29	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.71% African / African-American · 2,035/74,998 alleles

Filtering AF 2.62% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.58%

Overall 0.146% 2,353/1,613,950 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.71%	37
Middle Eastern	0.215%	466
Admixed American	0.198%	504
Remaining individualsnot grpmax-eligible	0.174%	573
South Asian	0.0143%	7,005
European (non-Finnish)	0.00542%	18,436

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.Lys480Gln
Coding: c.1438A>C
MANE Select: NM_001083
dbSNP: rs114790192
Type: single nucleotide variant
Location: chr4:119542593 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.32 · 50 PDB
Residue 480: the gaf 2 domain

Full PDE5A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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.Pro671= Benign ★★ same type
PDE5A p.Ala235Val Uncertain significance ★ ⚠ same type
PDE5A p.Ala282Val 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-lys480gln (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown