Is APRT p.Arg122Lys (c.365G>A) pathogenic?

APRT p.Arg122Lys (c.365G>A) is classified Uncertain significance in APRT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-12). AlphaMissense: likely benign (0.0882); Very rare (popmax 0.00167%, amr); Associated with adenine phosphoribosyltransferase deficiency.

What condition is associated with APRT p.Arg122Lys (c.365G>A)?

APRT p.Arg122Lys (c.365G>A) is associated with adenine phosphoribosyltransferase deficiency (ClinVar).

How common is APRT p.Arg122Lys (c.365G>A) in the general population?

APRT p.Arg122Lys (c.365G>A) is very rare (popmax 0.00167%, amr) (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.Arg122Lys (c.365G>A)?

AlphaMissense predicts likely benign (score 0.0882) — an in-silico prediction, not a clinical call.

APRT p.Arg122Lys

c.365G>A · VCV3581347

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0882 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

adenine phosphoribosyltransferase deficiency

Computational evidence

Protein change
AlphaMissense	0.0882	likely benign
REVEL	0.39	indeterminate
SaProt	LLR -6.89	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP -0.24, phastCons 0.84
Regional constraint	o/e 1.26	unconstrained · MANE · 2,198 bp · p 5.8e-05 · regional, not allelic
Overall
CADD	1.053	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,034 alleles

Overall 0.000274% 4/1,460,952 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,034
Remaining individualsnot grpmax-eligible	0.0016%	62,494
Finnishnot grpmax-eligible	0.00158%	63,184
European (non-Finnish)	8.47e-05%	1,179,994

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.Arg122Lys
Coding: c.365G>A
MANE Select: NM_000485
Type: single nucleotide variant
Location: chr16:88810105 (GRCh38)
Gene constraint: LOEUF 1.789 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.91 · 16 PDB
Residue 122: 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.Arg122= Conflicting classifications of pathogenicity ★ same residue
APRT p.Arg122Ser Uncertain significance ★ ⚠ 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-arg122lys (accessed [today's date]).

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