Is APRT p.Leu97fs (c.289_290del) pathogenic?

APRT p.Leu97fs (c.289290del) is classified Pathogenic in APRT (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-03). Ultra-rare (popmax 0.0164%, mid); Associated with adenine phosphoribosyltransferase deficiency.

What condition is associated with APRT p.Leu97fs (c.289_290del)?

APRT p.Leu97fs (c.289_290del) is associated with adenine phosphoribosyltransferase deficiency (ClinVar).

How common is APRT p.Leu97fs (c.289_290del) in the general population?

APRT p.Leu97fs (c.289_290del) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

How is Adenine phosphoribosyltransferase deficiency inherited?

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

APRT p.Leu97fs

c.289_290del · rs1437920638 · VCV988053

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

adenine phosphoribosyltransferase deficiency

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 3 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.12	GERP 1.6, phastCons 0.95
Overall
CADD	23.4	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

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000806% 13/1,612,076 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
Finnishnot grpmax-eligible	0.00161%	62,188
Remaining individualsnot grpmax-eligible	0.0016%	62,462
European (non-Finnish)	0.000848%	117,989

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: APRT
Protein: p.Leu97fs
Coding: c.289_290del
MANE Select: NM_000485
dbSNP: rs1437920638
Type: Microsatellite
Location: chr16:88810454 (GRCh38)
Gene constraint: LOEUF 1.789 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.91 · 16 PDB
Residue 97: a β-strand

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

Disease context

adenine phosphoribosyltransferase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Adenine phosphoribosyltransferase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Elderly, Infancy
Prevalence: 1-9 / 100 000 (Specific population)

Similar variants

APRT p.Phe174del Pathogenic/Likely pathogenic ★★ same condition
APRT p.Arg67Gln Likely pathogenic ★★ same condition
APRT p.Arg67Ter Pathogenic ★★ same condition
APRT p.Arg87Ter Pathogenic ★★ same condition
APRT p.Asp65Val Pathogenic ★★ same condition
APRT p.Gly133Arg Likely pathogenic ★★ same condition
APRT p.Gly63Asp Likely pathogenic ★★ same condition
APRT p.Met1Ile 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/aprt-p-leu97fs (accessed [today's date]).

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