Is PDE5A p.Glu119Val (c.356A>T) pathogenic?

PDE5A p.Glu119Val (c.356A>T) is classified Benign/Likely benign in PDE5A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-18). AlphaMissense: likely benign (0.0787); Low-frequency (popmax 2.06%, afr).

How common is PDE5A p.Glu119Val (c.356A>T) in the general population?

PDE5A p.Glu119Val (c.356A>T) is low-frequency (popmax 2.06%, afr) (gnomAD).

What do computational predictors say about PDE5A p.Glu119Val (c.356A>T)?

AlphaMissense predicts likely benign (score 0.0787) — an in-silico prediction, not a clinical call.

PDE5A p.Glu119Val

c.356A>T · rs76373430 · VCV716823

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0787 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.06%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0787	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -7.10	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 4.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 130 kb · p 1.5e-08 · regional, not allelic
Overall
CADD	21.4	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 2.06% African / African-American · 1,543/75,050 alleles

Filtering AF 1.97% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.94%

Overall 0.118% 1,912/1,614,170 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.06%	49
Remaining individualsnot grpmax-eligible	0.21%	477
Admixed American	0.17%	588
Middle Eastern	0.115%	866
European (non-Finnish)	0.0105%	9,516
South Asian	0.00549%	18,216

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.Glu119Val
Coding: c.356A>T
MANE Select: NM_001083
dbSNP: rs76373430
Type: single nucleotide variant
Location: chr4:119607094 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.32 · 50 PDB
Residue 119: a turn

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.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
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-glu119val (accessed [today's date]).

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