Is PDE12 p.Pro161Ser (c.481C>T) pathogenic?

PDE12 p.Pro161Ser (c.481C>T) is classified Uncertain significance in PDE12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-22). AlphaMissense: ambiguous (0.5467); Absent from gnomAD v4.1.

How common is PDE12 p.Pro161Ser (c.481C>T) in the general population?

PDE12 p.Pro161Ser (c.481C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDE12 p.Pro161Ser (c.481C>T)?

AlphaMissense predicts ambiguous (score 0.5467) — an in-silico prediction, not a clinical call.

PDE12 p.Pro161Ser

c.481C>T · VCV3887182

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5467 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5467	ambiguous
REVEL	0.144	moderately benign-leaning
SaProt	LLR -7.82	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 3,303 bp · p 0.0013 · regional, not allelic
Overall
CADD	23.7	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: PDE12
Protein: p.Pro161Ser
Coding: c.481C>T
MANE Select: NM_177966
Type: single nucleotide variant
Location: chr3:57556860 (GRCh38)
Gene constraint: LOEUF 0.757 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.45 · 3 PDB
Residue 161: an α-helix

Full PDE12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PDE12 p.Ala201Thr Uncertain significance ★ ⚠ same type
PDE12 p.Ala206Val Uncertain significance ★ ⚠ same type
PDE12 p.Ala322Pro Uncertain significance ★ ⚠ same type
PDE12 p.Ala404Val Uncertain significance ★ ⚠ same type
PDE12 p.Ala424Thr Uncertain significance ★ ⚠ same type
PDE12 p.Ala79Thr Uncertain significance ★ ⚠ same type
PDE12 p.Arg128Gly Uncertain significance ★ ⚠ same type
PDE12 p.Arg196Cys 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/pde12-p-pro161ser (accessed [today's date]).

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