Is APRT p.Pro17Ala (c.49C>G) pathogenic?

APRT p.Pro17Ala (c.49C>G) is classified Uncertain significance in APRT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-16). AlphaMissense: likely benign (0.1195); Very rare (popmax 0.00679%, afr); Associated with Inborn genetic diseases.

What condition is associated with APRT p.Pro17Ala (c.49C>G)?

APRT p.Pro17Ala (c.49C>G) is associated with Inborn genetic diseases, adenine phosphoribosyltransferase deficiency (ClinVar).

How common is APRT p.Pro17Ala (c.49C>G) in the general population?

APRT p.Pro17Ala (c.49C>G) is very rare (popmax 0.00679%, afr) (gnomAD).

What do computational predictors say about APRT p.Pro17Ala (c.49C>G)?

AlphaMissense predicts likely benign (score 0.1195) — an in-silico prediction, not a clinical call.

APRT p.Pro17Ala

c.49C>G · VCV3581364

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1195 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00679%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1195	likely benign
REVEL	0.629	indeterminate
SaProt	LLR -8.24	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 11	GERP 1.1, phastCons 1
Regional constraint	o/e 1.26	unconstrained · MANE · 2,198 bp · p 5.8e-05 · regional, not allelic
Overall
CADD	27.5	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 0.00679% African / African-American · 5/73,688 alleles

Filtering AF 0.00258% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00164%

Overall 0.000381% 6/1,572,758 alleles · very rare exomes 1/1,420,544 · genomes 5/152,214 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00679%	14,738
East Asian	0.00235%	42,634

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.Pro17Ala
Coding: c.49C>G
MANE Select: NM_000485
Type: single nucleotide variant
Location: chr16:88811851 (GRCh38)
Gene constraint: LOEUF 1.789 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.91 · 16 PDB
Residue 17: a β-strand

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

Also linked: adenine phosphoribosyltransferase deficiency

Similar variants

APRT p.Pro17Ser 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
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-pro17ala (accessed [today's date]).

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