Is APRT p.Ala37fs (c.108del) pathogenic?

APRT p.Ala37fs (c.108del) is classified Pathogenic in APRT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-08). Very rare (popmax 0.000125%).

How common is APRT p.Ala37fs (c.108del) in the general population?

APRT p.Ala37fs (c.108del) is very rare (popmax 0.000125%) (gnomAD).

APRT p.Ala37fs

c.108del · rs1909145179 · VCV3021749

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000125%)

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 2 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.97	GERP -0.025, phastCons 0.001

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000125%

Overall 0.000125% 2/1,601,138 alleles · very rare exomes 2/1,448,828 · genomes 0/152,310 · joint denominator

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.Ala37fs
Coding: c.108del
MANE Select: NM_000485
dbSNP: rs1909145179
Type: Deletion
Location: chr16:88811629 (GRCh38)
Gene constraint: LOEUF 1.789 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.91 · 16 PDB
Residue 37: an α-helix

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

Similar variants

APRT p.Ala37Val Uncertain significance ★ ⚠ same residue
APRT p.Thr96fs Pathogenic/Likely pathogenic ★★ same type
APRT c.401-40_401-25del Likely pathogenic ★ same type
APRT p.Glu158del Pathogenic ★ same type
APRT p.Glu5fs Likely pathogenic ★ same type
APRT p.Gly94fs Pathogenic ★ same type
APRT p.Leu130fs Pathogenic ★ same type
APRT p.Leu162del Likely pathogenic ★ same type

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-ala37fs (accessed [today's date]).

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