Is APRT p.Pro31Leu (c.92C>T) pathogenic?

APRT p.Pro31Leu (c.92C>T) is classified Uncertain significance in APRT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-03). AlphaMissense: ambiguous (0.5608); Ultra-rare (popmax 0.0497%, afr).

How common is APRT p.Pro31Leu (c.92C>T) in the general population?

APRT p.Pro31Leu (c.92C>T) is ultra-rare (popmax 0.0497%, afr) (gnomAD).

What do computational predictors say about APRT p.Pro31Leu (c.92C>T)?

AlphaMissense predicts ambiguous (score 0.5608) — an in-silico prediction, not a clinical call.

APRT p.Pro31Leu

c.92C>T · rs149476467 · VCV1900905

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5608 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0497%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5608	ambiguous
REVEL	0.708	pathogenic-leaning
SaProt	LLR -12.08	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.2, phastCons 1
Regional constraint	o/e 1.26	unconstrained · MANE · 2,198 bp · p 5.8e-05 · regional, not allelic
Overall
CADD	24.8	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 0.0497% African / African-American · 37/74,510 alleles

Filtering AF 0.037% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0327%

Overall 0.00257% 41/1,595,984 alleles · ultra-rare exomes 19/1,443,644 · genomes 22/152,340 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0497%	2,014
Admixed American	0.00514%	19,450
South Asian	0.00113%	88,566

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.Pro31Leu
Coding: c.92C>T
MANE Select: NM_000485
dbSNP: rs149476467
Type: single nucleotide variant
Location: chr16:88811645 (GRCh38)
Gene constraint: LOEUF 1.789 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.91 · 16 PDB
Residue 31: an α-helix

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

Similar variants

APRT p.Pro31Ala Uncertain significance ★ ⚠ same residue
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

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-pro31leu (accessed [today's date]).

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