Is NAPRT p.Arg73Gln (c.218G>A) pathogenic?

NAPRT p.Arg73Gln (c.218G>A) is classified Likely benign in NAPRT (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-19). AlphaMissense: likely benign (0.065); Rare (popmax 0.316%, afr).

How common is NAPRT p.Arg73Gln (c.218G>A) in the general population?

NAPRT p.Arg73Gln (c.218G>A) is rare (popmax 0.316%, afr) (gnomAD).

What do computational predictors say about NAPRT p.Arg73Gln (c.218G>A)?

AlphaMissense predicts likely benign (score 0.065) — an in-silico prediction, not a clinical call.

NAPRT p.Arg73Gln

c.218G>A · rs11990768 · VCV734151

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.065 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.316%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.065	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -5.23	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.8	GERP -2.6
Regional constraint	o/e 1.12	unconstrained · MANE · 3,477 bp · p 0.0014 · regional, not allelic
Overall
CADD	10.06	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 0.316% African / African-American · 225/71,120 alleles

Filtering AF 0.282% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.269%

Overall 0.0171% 261/1,522,334 alleles · rare exomes 129/1,370,058 · genomes 132/152,276 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.316%	316
Remaining individualsnot grpmax-eligible	0.0221%	4,516
Admixed American	0.0218%	4,577
Middle Eastern	0.0207%	4,832
European (non-Finnish)	0.00105%	95,200

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: NAPRT
Protein: p.Arg73Gln
Coding: c.218G>A
MANE Select: NM_145201
dbSNP: rs11990768
Type: single nucleotide variant
Location: chr8:143578101 (GRCh38)
Gene constraint: LOEUF 1.486 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.94 · 1 PDB

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

Similar variants

NAPRT c.1447-7C>G Benign ★★ same type
NAPRT p.Asp320= Benign ★★ same type
NAPRT p.Pro117= Benign/Likely benign ★★ same type
NAPRT p.Ala13Gly Uncertain significance ★ ⚠ same type
NAPRT p.Ala159Thr Uncertain significance ★ ⚠ same type
NAPRT p.Ala231Val Uncertain significance ★ ⚠ same type
NAPRT p.Ala234Pro Uncertain significance ★ ⚠ same type
NAPRT p.Ala23Thr Uncertain significance ★ ⚠ 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/naprt-p-arg73gln (accessed [today's date]).

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