Is PDE3B p.Cys792Arg (c.2374T>C) pathogenic?

PDE3B p.Cys792Arg (c.2374T>C) is classified Uncertain significance in PDE3B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-11). AlphaMissense: likely benign (0.2645); Ultra-rare (popmax 0.03%, amr).

How common is PDE3B p.Cys792Arg (c.2374T>C) in the general population?

PDE3B p.Cys792Arg (c.2374T>C) is ultra-rare (popmax 0.03%, amr) (gnomAD).

What do computational predictors say about PDE3B p.Cys792Arg (c.2374T>C)?

AlphaMissense predicts likely benign (score 0.2645) — an in-silico prediction, not a clinical call.

PDE3B p.Cys792Arg

c.2374T>C · rs1350442610 · VCV2375771

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2645 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.03%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2645	likely benign
REVEL	0.683	pathogenic-leaning
SaProt	LLR -6.90	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 39 kb · p 1.8e-08 · regional, not allelic
Overall
CADD	26.8	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 0.03% Admixed American · 18/60,000 alleles

Filtering AF 0.0194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.016%

Overall 0.00235% 38/1,613,986 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.03%	3,333
Remaining individualsnot grpmax-eligible	0.0096%	10,414
European (non-Finnish)	0.00119%	84,283

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: PDE3B
Protein: p.Cys792Arg
Coding: c.2374T>C
MANE Select: NM_000922
dbSNP: rs1350442610
Type: single nucleotide variant
Location: chr11:14843880 (GRCh38)
Gene constraint: LOEUF 0.955 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.10 · 4 PDB
Residue 792: the pdease domain

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

Similar variants

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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-cys792arg (accessed [today's date]).

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