Is APRT p.Arg67Gln (c.200G>A) pathogenic?

APRT p.Arg67Gln (c.200G>A) is classified Likely pathogenic in APRT (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-02-25). AlphaMissense: likely pathogenic (0.8812); Very rare (popmax 0.0022%, sas); Associated with adenine phosphoribosyltransferase deficiency.

What condition is associated with APRT p.Arg67Gln (c.200G>A)?

APRT p.Arg67Gln (c.200G>A) is associated with adenine phosphoribosyltransferase deficiency (ClinVar).

How common is APRT p.Arg67Gln (c.200G>A) in the general population?

APRT p.Arg67Gln (c.200G>A) is very rare (popmax 0.0022%, 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.Arg67Gln (c.200G>A)?

AlphaMissense predicts likely pathogenic (score 0.8812) — an in-silico prediction, not a clinical call.

APRT p.Arg67Gln

c.200G>A · rs762509151 · VCV988046

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.8812 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

adenine phosphoribosyltransferase deficiency

Computational evidence

Protein change
AlphaMissense	0.8812	likely pathogenic ✓ concordant with ClinVar
REVEL	0.917	moderately pathogenic-leaning
SaProt	LLR -13.47	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 7.5	GERP 1.7, phastCons 1
Regional constraint	o/e 1.26	unconstrained · MANE · 2,198 bp · p 5.8e-05 · regional, not allelic
Overall
CADD	34.0	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 0.0022% South Asian · 2/90,902 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.00048% 7/1,459,378 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,451
Admixed American	0.00167%	59,910
Remaining individualsnot grpmax-eligible	0.0016%	62,428
European (non-Finnish)	0.000254%	393,258

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.Arg67Gln
Coding: c.200G>A
MANE Select: NM_000485
dbSNP: rs762509151
Type: single nucleotide variant
Location: chr16:88810544 (GRCh38)
Gene constraint: LOEUF 1.789 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.91 · 16 PDB
Residue 67: 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.Arg67Ter Pathogenic ★★ same residue
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
APRT p.Trp98Ter 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-arg67gln (accessed [today's date]).

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