Is APRT p.Leu143Pro (c.428T>C) pathogenic?

APRT p.Leu143Pro (c.428T>C) is classified Pathogenic in APRT (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-09-01). AlphaMissense: likely pathogenic (0.8641); Absent from gnomAD v4.1; Associated with adenine phosphoribosyltransferase deficiency.

What condition is associated with APRT p.Leu143Pro (c.428T>C)?

APRT p.Leu143Pro (c.428T>C) is associated with adenine phosphoribosyltransferase deficiency (ClinVar).

How common is APRT p.Leu143Pro (c.428T>C) in the general population?

APRT p.Leu143Pro (c.428T>C) is absent from gnomAD v4.1 (gnomAD).

How is Adenine phosphoribosyltransferase deficiency inherited?

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

What do computational predictors say about APRT p.Leu143Pro (c.428T>C)?

AlphaMissense predicts likely pathogenic (score 0.8641) — an in-silico prediction, not a clinical call.

APRT p.Leu143Pro

c.428T>C · rs1909040577 · VCV988064

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8641 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

adenine phosphoribosyltransferase deficiency

Computational evidence

Protein change
AlphaMissense	0.8641	likely pathogenic ✓ concordant with ClinVar
REVEL	0.911	moderately pathogenic-leaning
SaProt	LLR -16.21	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 1.26	unconstrained · MANE · 2,198 bp · p 5.8e-05 · regional, not allelic
Overall
CADD	24.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: APRT
Protein: p.Leu143Pro
Coding: c.428T>C
MANE Select: NM_000485
dbSNP: rs1909040577
Type: single nucleotide variant
Location: chr16:88809813 (GRCh38)
Gene constraint: LOEUF 1.789 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.91 · 16 PDB
Residue 143: an α-helix

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.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
APRT p.Met1Val 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-leu143pro (accessed [today's date]).

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