Is PDE3B p.Phe131Cys (c.392T>G) pathogenic?

PDE3B p.Phe131Cys (c.392T>G) is classified Uncertain significance in PDE3B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-07). AlphaMissense: likely pathogenic (0.7599); Absent from gnomAD v4.1.

How common is PDE3B p.Phe131Cys (c.392T>G) in the general population?

PDE3B p.Phe131Cys (c.392T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDE3B p.Phe131Cys (c.392T>G)?

AlphaMissense predicts likely pathogenic (score 0.7599) — an in-silico prediction, not a clinical call.

PDE3B p.Phe131Cys

c.392T>G · rs2494129287 · VCV2265742

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7599 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7599	likely pathogenic
REVEL	0.559	indeterminate
SaProt	LLR -5.89	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.1, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 187 kb · p 1.5e-07 · regional, not allelic
Overall
CADD	27.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PDE3B
Protein: p.Phe131Cys
Coding: c.392T>G
MANE Select: NM_000922
dbSNP: rs2494129287
Type: single nucleotide variant
Location: chr11:14644467 (GRCh38)
Gene constraint: LOEUF 0.955 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.10 · 4 PDB

Full PDE3B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CYP2R1 p.Gly450Arg Uncertain significance ★★ ⚠ same type
CYP2R1 p.Gly91Asp Uncertain significance ★★ ⚠ same type
CYP2R1 p.His381Arg Uncertain significance ★★ ⚠ same type
CYP2R1 p.Ile332Thr Uncertain significance ★★ ⚠ same type
CYP2R1 p.Met284Ile Uncertain significance ★★ ⚠ same type
CYP2R1 p.Pro36Leu Uncertain significance ★★ ⚠ same type
CYP2R1 p.Tyr431His Uncertain significance ★★ ⚠ same type
PDE3B p.Thr137Ala 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/pde3b-p-phe131cys (accessed [today's date]).

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