Is APRT p.Leu176fs (c.526_530del) pathogenic?

APRT p.Leu176fs (c.526530del) is classified Pathogenic in APRT (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-09-01). Very rare (popmax 0.0022%, sas); Associated with adenine phosphoribosyltransferase deficiency.

What condition is associated with APRT p.Leu176fs (c.526_530del)?

APRT p.Leu176fs (c.526_530del) is associated with adenine phosphoribosyltransferase deficiency (ClinVar).

How common is APRT p.Leu176fs (c.526_530del) in the general population?

APRT p.Leu176fs (c.526_530del) is very rare (popmax 0.0022%, sas) (gnomAD).

How is Adenine phosphoribosyltransferase deficiency inherited?

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

APRT p.Leu176fs

c.526_530del · rs755380873 · VCV988023

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

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	escapes	premature termination codon in the last exon (5 of 5) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.01	GERP -2.3, phastCons 0.79

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,084 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000137% 2/1,461,074 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: APRT
Protein: p.Leu176fs
Coding: c.526_530del
MANE Select: NM_000485
dbSNP: rs755380873
Type: Deletion
Location: chr16:88809711 (GRCh38)
Gene constraint: LOEUF 1.789 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.91 · 16 PDB
Residue 176: 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.Leu176Phe Pathogenic ⚠ same residue
APRT p.Thr96fs Pathogenic/Likely pathogenic ★★ same condition
APRT c.401-40_401-25del Likely pathogenic ★ same condition
APRT p.Glu158del Pathogenic ★ same condition
APRT p.Glu5fs Likely pathogenic ★ same condition
APRT p.Phe39fs Likely pathogenic ★ same condition
APRT p.Ser175del Pathogenic ★ same condition
APRT c.184_187+22del 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-leu176fs (accessed [today's date]).

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