Is APRT p.Gln178His (c.534G>C) pathogenic?

APRT p.Gln178His (c.534G>C) is classified Uncertain significance in APRT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-13). AlphaMissense: ambiguous (0.3459); Absent from gnomAD v4.1; Associated with adenine phosphoribosyltransferase deficiency.

What condition is associated with APRT p.Gln178His (c.534G>C)?

APRT p.Gln178His (c.534G>C) is associated with adenine phosphoribosyltransferase deficiency (ClinVar).

How common is APRT p.Gln178His (c.534G>C) in the general population?

APRT p.Gln178His (c.534G>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.Gln178His (c.534G>C)?

AlphaMissense predicts ambiguous (score 0.3459) — an in-silico prediction, not a clinical call.

APRT p.Gln178His

c.534G>C · VCV3581338

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3459 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

adenine phosphoribosyltransferase deficiency

Computational evidence

Protein change
AlphaMissense	0.3459	ambiguous
REVEL	0.616	indeterminate
SaProt	LLR -9.80	tolerated
Splicing
SpliceAI	Δ0.77	acceptor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -0.018	GERP 0.44, phastCons 0.74
Regional constraint	o/e 1.26	unconstrained · MANE · 2,198 bp · p 5.8e-05 · regional, not allelic
Overall
CADD	19.38	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.Gln178His
Coding: c.534G>C
MANE Select: NM_000485
Type: single nucleotide variant
Location: chr16:88809707 (GRCh38)
Gene constraint: LOEUF 1.789 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.91 · 16 PDB
Residue 178: 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.Gln178Ter Pathogenic same residue
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-gln178his (accessed [today's date]).

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