Is APRT p.Pro172Ala (c.514C>G) pathogenic?

APRT p.Pro172Ala (c.514C>G) is classified Uncertain significance in APRT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: likely benign (0.1068); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with APRT p.Pro172Ala (c.514C>G)?

APRT p.Pro172Ala (c.514C>G) is associated with Inborn genetic diseases (ClinVar).

How common is APRT p.Pro172Ala (c.514C>G) in the general population?

APRT p.Pro172Ala (c.514C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about APRT p.Pro172Ala (c.514C>G)?

AlphaMissense predicts likely benign (score 0.1068) — an in-silico prediction, not a clinical call.

APRT p.Pro172Ala

c.514C>G · rs781239221 · VCV3128096

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1068 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1068	likely benign
REVEL	0.373	indeterminate
SaProt	LLR -10.39	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	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	22.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: APRT
Protein: p.Pro172Ala
Coding: c.514C>G
MANE Select: NM_000485
dbSNP: rs781239221
Type: single nucleotide variant
Location: chr16:88809727 (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.Asp3Gly 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-pro172ala (accessed [today's date]).

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