Is APRT p.Arg89Gln (c.266G>A) pathogenic?

APRT p.Arg89Gln (c.266G>A) is classified Benign/Likely benign in APRT (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-24). AlphaMissense: likely benign (0.1144); Rare (popmax 0.407%, sas); Associated with adenine phosphoribosyltransferase deficiency.

What condition is associated with APRT p.Arg89Gln (c.266G>A)?

APRT p.Arg89Gln (c.266G>A) is associated with adenine phosphoribosyltransferase deficiency (ClinVar).

How common is APRT p.Arg89Gln (c.266G>A) in the general population?

APRT p.Arg89Gln (c.266G>A) is rare (popmax 0.407%, sas) (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.Arg89Gln (c.266G>A)?

AlphaMissense predicts likely benign (score 0.1144) — an in-silico prediction, not a clinical call.

APRT p.Arg89Gln

c.266G>A · rs150156607 · VCV884724

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1144 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.407%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

adenine phosphoribosyltransferase deficiency

Computational evidence

Protein change
AlphaMissense	0.1144	likely benign
REVEL	0.418	indeterminate
SaProt	LLR -7.07	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.12	GERP 0.46
Regional constraint	o/e 1.26	unconstrained · MANE · 2,198 bp · p 5.8e-05 · regional, not allelic
Overall
CADD	19.79	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

Grpmax group 0.407% South Asian · 371/91,074 alleles

Filtering AF 0.373% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.36%

Overall 0.114% 1,841/1,612,298 alleles · rare exomes 1,744/1,460,010 · genomes 97/152,288 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.407%	245
European (non-Finnish)	0.118%	849
Remaining individualsnot grpmax-eligible	0.0864%	1,157
African / African-American	0.0227%	4,415
Middle Eastern	0.0165%	6,060
Admixed American	0.01%	10,002
East Asian	0.00223%	44,872
Finnishnot grpmax-eligible	0.0016%	62,316

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.Arg89Gln
Coding: c.266G>A
MANE Select: NM_000485
dbSNP: rs150156607
Type: single nucleotide variant
Location: chr16:88810478 (GRCh38)
Gene constraint: LOEUF 1.789 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.91 · 16 PDB

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.Arg89Trp Uncertain significance ★★ ⚠ same residue
APRT p.Arg89= Likely benign ★ 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

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-arg89gln (accessed [today's date]).

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