Is PDCD10 p.Leu44Pro (c.131T>C) pathogenic?

PDCD10 p.Leu44Pro (c.131T>C) is classified Uncertain significance in PDCD10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-26). AlphaMissense: likely pathogenic (0.9996); Absent from gnomAD v4.1; Associated with cerebral cavernous malformation 3.

What condition is associated with PDCD10 p.Leu44Pro (c.131T>C)?

PDCD10 p.Leu44Pro (c.131T>C) is associated with cerebral cavernous malformation 3 (ClinVar).

How common is PDCD10 p.Leu44Pro (c.131T>C) in the general population?

PDCD10 p.Leu44Pro (c.131T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDCD10 p.Leu44Pro (c.131T>C)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

PDCD10 p.Leu44Pro

c.131T>C · VCV4747373

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cerebral cavernous malformation 3

Computational evidence

Protein change
AlphaMissense	0.9996	likely pathogenic · top 6% in PDCD10
REVEL	0.771	pathogenic-leaning
SaProt	LLR -16.00	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 36 kb · p 3.1e-06 · regional, not allelic
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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: PDCD10
Protein: p.Leu44Pro
Coding: c.131T>C
MANE Select: NM_007217
Type: single nucleotide variant
Location: chr3:167704861 (GRCh38)
Gene constraint: LOEUF 0.924 · pLI 0.64 (gnomAD)
Structure: AlphaFold pLDDT 90.82 · 10 PDB
Residue 44: an α-helix

Full PDCD10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cerebral cavernous malformation 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PDCD10 p.Leu44Arg Uncertain significance ★★ ⚠ same residue
PDCD10 p.Leu44_Arg45insTer Pathogenic ★ same residue
PDCD10 c.396-2A>G Pathogenic ★★ same condition
PDCD10 c.474+5G>A Pathogenic/Likely pathogenic ★★ same condition
PDCD10 c.557+1G>A Pathogenic ★★ same condition
PDCD10 p.Arg108Ter Pathogenic ★★ same condition
PDCD10 p.Arg196Ter Pathogenic ★★ same condition
PDCD10 p.Arg35Ter Pathogenic ★★ same condition

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/pdcd10-p-leu44pro (accessed [today's date]).

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