Is APRT p.Glu118Gln (c.352G>C) pathogenic?

APRT p.Glu118Gln (c.352G>C) is classified Uncertain significance in APRT (ClinVar, Single submitter, 2 submitters; last evaluated 2023-08-19). AlphaMissense: likely benign (0.0743); Ultra-rare (popmax 0.0116%, nfe); Associated with adenine phosphoribosyltransferase deficiency.

What condition is associated with APRT p.Glu118Gln (c.352G>C)?

APRT p.Glu118Gln (c.352G>C) is associated with adenine phosphoribosyltransferase deficiency (ClinVar).

How common is APRT p.Glu118Gln (c.352G>C) in the general population?

APRT p.Glu118Gln (c.352G>C) is ultra-rare (popmax 0.0116%, nfe) (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.Glu118Gln (c.352G>C)?

AlphaMissense predicts likely benign (score 0.0743) — an in-silico prediction, not a clinical call.

APRT p.Glu118Gln

c.352G>C · rs370665100 · VCV988056

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0743 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0116%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

adenine phosphoribosyltransferase deficiency

Computational evidence

Protein change
AlphaMissense	0.0743	likely benign
REVEL	0.763	pathogenic-leaning
SaProt	LLR -8.10	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 0.46, phastCons 1
Regional constraint	o/e 1.26	unconstrained · MANE · 2,198 bp · p 5.8e-05 · regional, not allelic
Overall
CADD	17.18	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 0.0116% European (non-Finnish) · 137/1,180,018 alleles

Filtering AF 0.01% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00939%

Overall 0.00886% 143/1,613,162 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0116%	8,613
Remaining individualsnot grpmax-eligible	0.0048%	20,826
Finnishnot grpmax-eligible	0.00317%	31,573
African / African-American	0.00133%	74,918

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.Glu118Gln
Coding: c.352G>C
MANE Select: NM_000485
dbSNP: rs370665100
Type: single nucleotide variant
Location: chr16:88810118 (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.Glu118= 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
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-glu118gln (accessed [today's date]).

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