Is AMPD2 p.Gln107Ter (c.319C>T) pathogenic?

AMPD2 p.Gln107Ter (c.319C>T) is classified Pathogenic in AMPD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-11). Absent from gnomAD v4.1; Associated with hereditary spastic paraplegia 63.

What condition is associated with AMPD2 p.Gln107Ter (c.319C>T)?

AMPD2 p.Gln107Ter (c.319C>T) is associated with hereditary spastic paraplegia 63, pontocerebellar hypoplasia type 9 (ClinVar).

How common is AMPD2 p.Gln107Ter (c.319C>T) in the general population?

AMPD2 p.Gln107Ter (c.319C>T) is absent from gnomAD v4.1 (gnomAD).

How is Autosomal recessive spastic paraplegia type 63 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

AMPD2 p.Gln107Ter

c.319C>T · rs2524398223 · VCV2004862

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary spastic paraplegia 63

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 19
REVEL	0.717	pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

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

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: AMPD2
Protein: p.Gln107Ter
Coding: c.319C>T
MANE Select: NM_001368809
dbSNP: rs2524398223
Type: single nucleotide variant
Location: chr1:109625758 (GRCh38)
Gene constraint: LOEUF 0.705 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.28 · 5 PDB

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

Disease context

hereditary spastic paraplegia 63 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pontocerebellar hypoplasia type 9

For Autosomal recessive spastic paraplegia type 63 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

AMPD2 p.Gln107= Likely benign ★ same residue
AMPD2 c.1698+1G>A Pathogenic/Likely pathogenic ★★ same condition
AMPD2 p.Arg353Ter Pathogenic/Likely pathogenic ★★ same condition
AMPD2 p.Arg449Ter Pathogenic/Likely pathogenic ★★ same condition
AMPD2 p.Arg620His Pathogenic/Likely pathogenic ★★ same condition
AMPD2 p.Arg789His Likely pathogenic ★★ same condition
AMPD2 p.Glu174Ter Pathogenic/Likely pathogenic ★★ same condition
AMPD2 c.1080+3G>A Uncertain significance ★★ 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-gln107ter (accessed [today's date]).

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