Is ADPRS p.Thr79Pro (c.235A>C) pathogenic?

ADPRS p.Thr79Pro (c.235A>C) is classified Pathogenic/Likely pathogenic in ADPRS (ClinVar, Multiple submitters, 4 submitters; last evaluated 2020-09-30). AlphaMissense: likely pathogenic (0.9715); Very rare (popmax 8.47e-05%, nfe); Associated with neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures.

How common is ADPRS p.Thr79Pro (c.235A>C) in the general population?

ADPRS p.Thr79Pro (c.235A>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ADPRS p.Thr79Pro (c.235A>C)?

AlphaMissense predicts likely pathogenic (score 0.9715) — an in-silico prediction, not a clinical call.

ADPRS p.Thr79Pro

Q: What condition is associated with ADPRS p.Thr79Pro (c.235A>C)?

ADPRS p.Thr79Pro (c.235A>C) is associated with neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures (ClinVar).

Q: How is Childhood-onset stress-induced neurodegenerative ataxia-seizure syndrome inherited?

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

c.235A>C · rs1557733311 · VCV590300

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9715 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures

Computational evidence

Protein change
AlphaMissense	0.9715	likely pathogenic ✓ concordant with ClinVar
REVEL	0.788	moderately pathogenic-leaning
SaProt	LLR -11.01	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 1.6, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 4,478 bp · p 0.95 · regional, not allelic
Overall
CADD	29.8	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 8.47e-05% European (non-Finnish) · 1/1,180,014 alleles

Overall 6.84e-05% 1/1,461,824 alleles · very rare

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: ADPRS
Protein: p.Thr79Pro
Coding: c.235A>C
MANE Select: NM_017825
dbSNP: rs1557733311
Type: single nucleotide variant
Location: chr1:36091267 (GRCh38)
Gene constraint: LOEUF 1.155 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.70 · 14 PDB
Residue 79: a UniProt-annotated variant site (in condsias; severely reduced protein levels in patient fibroblasts; decreased stability and reduced tm; reduced alpha-helix content and altered secondary structure detected by circular dichroism spectroscopy); an α-helix

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

Disease context

neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Childhood-onset stress-induced neurodegenerative ataxia-seizure syndrome (Orphanet):

Inheritance: Autosomal recessive

Similar variants

ADPRS p.Gln106Ter Pathogenic/Likely pathogenic ★★ same condition
ADPRS p.Ser177Leu Likely pathogenic ★★ same condition
ADPRS p.Val335Gly Pathogenic/Likely pathogenic ★★ same condition
ADPRS p.Arg175Trp Uncertain significance ★★ ⚠ same condition
ADPRS p.Tyr164Cys Uncertain significance ★★ ⚠ same condition
ADPRS p.Val46Phe Uncertain significance ★★ ⚠ same condition
ADPRS p.Gln194Ter Pathogenic ★ same condition
ADPRS p.Gln214Ter 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/adprs-p-thr79pro (accessed [today's date]).

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