Is APRT p.Asp3Gly (c.8A>G) pathogenic?

APRT p.Asp3Gly (c.8A>G) is classified Uncertain significance in APRT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-30). AlphaMissense: likely benign (0.0859); Ultra-rare (popmax 0.0124%, afr); Associated with Inborn genetic diseases.

What condition is associated with APRT p.Asp3Gly (c.8A>G)?

APRT p.Asp3Gly (c.8A>G) is associated with Inborn genetic diseases (ClinVar).

How common is APRT p.Asp3Gly (c.8A>G) in the general population?

APRT p.Asp3Gly (c.8A>G) is ultra-rare (popmax 0.0124%, afr) (gnomAD).

What do computational predictors say about APRT p.Asp3Gly (c.8A>G)?

AlphaMissense predicts likely benign (score 0.0859) — an in-silico prediction, not a clinical call.

APRT p.Asp3Gly

c.8A>G · VCV4583330

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0859 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0124%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0859	likely benign
REVEL	0.215	benign-leaning
SaProt	LLR -8.44	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 0.18, phastCons 1
Regional constraint	o/e 1.26	unconstrained · MANE · 2,198 bp · p 5.8e-05 · regional, not allelic
Overall
CADD	20.0	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 0.0124% African / African-American · 9/72,746 alleles

Filtering AF 0.0064% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0048%

Overall 0.000837% 13/1,554,014 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0124%	8,083
South Asian	0.00237%	42,218
Remaining individualsnot grpmax-eligible	0.00166%	60,224
European (non-Finnish)	8.68e-05%	1,152,214

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.Asp3Gly
Coding: c.8A>G
MANE Select: NM_000485
Type: single nucleotide variant
Location: chr16:88811892 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

APRT p.Ala138Thr Uncertain significance ★★ ⚠ same condition
APRT p.Arg89Trp Uncertain significance ★★ ⚠ same condition
APRT p.Asp59Asn Uncertain significance ★★ ⚠ same condition
APRT p.Ile61Val Uncertain significance ★★ ⚠ same condition
APRT p.Leu129Arg Uncertain significance ★★ ⚠ same condition
APRT p.Pro17Ala Uncertain significance ★★ ⚠ same condition
APRT p.Ala116Val Uncertain significance ★ ⚠ same condition
APRT p.Gln7Arg Uncertain significance ★ ⚠ 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-asp3gly (accessed [today's date]).

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