Is APRT p.Leu85fs (c.254del) pathogenic?

APRT p.Leu85fs (c.254del) is classified Pathogenic in APRT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). Very rare (popmax 0.00133%, afr).

How common is APRT p.Leu85fs (c.254del) in the general population?

APRT p.Leu85fs (c.254del) is very rare (popmax 0.00133%, afr) (gnomAD).

APRT p.Leu85fs

c.254del · VCV4694130

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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 2.3	GERP 0.46, phastCons 1
Overall
CADD	32.0	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

Grpmax group 0.00133% African / African-American · 1/74,926 alleles

Overall 0.000657% 1/152,180 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.Leu85fs
Coding: c.254del
MANE Select: NM_000485
Type: Deletion
Location: chr16:88810490 (GRCh38)
Gene constraint: LOEUF 1.789 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.91 · 16 PDB
Residue 85: a β-strand

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

Similar variants

APRT p.Thr96fs Pathogenic/Likely pathogenic ★★ same type
APRT c.401-40_401-25del Likely pathogenic ★ same type
APRT p.Ala37fs 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-leu85fs (accessed [today's date]).

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