Is APRT p.Gln121Arg (c.362A>G) pathogenic?

APRT p.Gln121Arg (c.362A>G) is classified Likely benign in APRT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). AlphaMissense: likely benign (0.1937); Rare (popmax 0.541%, afr).

How common is APRT p.Gln121Arg (c.362A>G) in the general population?

APRT p.Gln121Arg (c.362A>G) is rare (popmax 0.541%, afr) (gnomAD).

What do computational predictors say about APRT p.Gln121Arg (c.362A>G)?

AlphaMissense predicts likely benign (score 0.1937) — an in-silico prediction, not a clinical call.

APRT p.Gln121Arg

c.362A>G · rs8191494 · VCV732386

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1937 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.541%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1937	likely benign
REVEL	0.598	indeterminate
SaProt	LLR -9.50	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 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 1.26	unconstrained · MANE · 2,198 bp · p 5.8e-05 · regional, not allelic
Overall
CADD	23.8	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 0.541% African / African-American · 406/75,052 alleles

Filtering AF 0.498% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.48%

Overall 0.0287% 463/1,613,306 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.541%	185
Admixed American	0.0416%	2,401
Remaining individualsnot grpmax-eligible	0.0416%	2,404
Middle Eastern	0.0165%	6,060
South Asian	0.0011%	91,086
European (non-Finnish)	0.000339%	294,998

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.Gln121Arg
Coding: c.362A>G
MANE Select: NM_000485
dbSNP: rs8191494
Type: single nucleotide variant
Location: chr16:88810108 (GRCh38)
Gene constraint: LOEUF 1.789 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.91 · 16 PDB
Residue 121: a UniProt-annotated variant site (in)

Full APRT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APRT p.Arg67Gln Likely pathogenic ★★ same type
APRT p.Arg67Ter Pathogenic ★★ same type
APRT p.Arg87Ter Pathogenic ★★ same type
APRT p.Asp65Val Pathogenic ★★ same type
APRT p.Gly133Arg Likely pathogenic ★★ same type
APRT p.Gly63Asp Likely pathogenic ★★ same type
APRT p.Met1Ile Pathogenic ★★ same type
APRT p.Met1Val Pathogenic ★★ same type

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-gln121arg (accessed [today's date]).

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