Is AMPD2 p.Pro442fs (c.1325del) pathogenic?

AMPD2 p.Pro442fs (c.1325del) is classified Likely pathogenic in AMPD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-21). Associated with pontocerebellar hypoplasia type 9.

What condition is associated with AMPD2 p.Pro442fs (c.1325del)?

AMPD2 p.Pro442fs (c.1325del) is associated with pontocerebellar hypoplasia type 9, hereditary spastic paraplegia 63 (ClinVar).

AMPD2 p.Pro442fs

c.1325del · VCV3896775

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

pontocerebellar hypoplasia type 9

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 12 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: AMPD2
Protein: p.Pro442fs
Coding: c.1325del
MANE Select: NM_001368809
Type: Deletion
Location: chr1:109628411 (GRCh38)
Gene constraint: LOEUF 0.705 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.28 · 5 PDB
Residue 442: an α-helix

Full AMPD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

pontocerebellar hypoplasia type 9 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary spastic paraplegia 63

Similar variants

AMPD2 p.Pro442= Likely benign ★★ same residue
AMPD2 p.Gly35fs Pathogenic/Likely pathogenic ★★ same condition
AMPD2 p.Leu216fs Pathogenic/Likely pathogenic ★★ same condition
AMPD2 c.1408-3_1418del Likely pathogenic ★ same condition
AMPD2 p.Ala89fs Pathogenic ★ same condition
AMPD2 p.Gln101fs Likely pathogenic ★ same condition
AMPD2 p.Lys14fs Pathogenic ★ same condition
AMPD2 p.Pro90fs Likely 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/ampd2-p-pro442fs (accessed [today's date]).

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