Is APRT p.Cys153= (c.459C>T) pathogenic?

APRT p.Cys153= (c.459C>T) is classified Likely benign in APRT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-12-21). Ultra-rare (popmax 0.0736%, sas); Associated with adenine phosphoribosyltransferase deficiency.

What condition is associated with APRT p.Cys153= (c.459C>T)?

APRT p.Cys153= (c.459C>T) is associated with adenine phosphoribosyltransferase deficiency (ClinVar).

How common is APRT p.Cys153= (c.459C>T) in the general population?

APRT p.Cys153= (c.459C>T) is ultra-rare (popmax 0.0736%, sas) (gnomAD).

How is Adenine phosphoribosyltransferase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

APRT p.Cys153=

c.459C>T · rs375131814 · VCV797738

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0736%, sas)

Conditions

adenine phosphoribosyltransferase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.9	GERP -3.2
Overall
CADD	2.921	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0736% South Asian · 67/91,088 alleles

Filtering AF 0.0593% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0542%

Overall 0.00533% 86/1,613,182 alleles · ultra-rare exomes 76/1,460,858 · genomes 10/152,324 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0736%	1,360
African / African-American	0.008%	12,508
Remaining individualsnot grpmax-eligible	0.0048%	20,832
European (non-Finnish)	0.000847%	118,000

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.Cys153=
Coding: c.459C>T
MANE Select: NM_000485
dbSNP: rs375131814
Type: single nucleotide variant
Location: chr16:88809782 (GRCh38)
Gene constraint: LOEUF 1.789 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.91 · 16 PDB
Residue 153: a UniProt-annotated variant site (in aprtd); a β-strand

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

Disease context

adenine phosphoribosyltransferase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Adenine phosphoribosyltransferase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Elderly, Infancy
Prevalence: 1-9 / 100 000 (Specific population)

Similar variants

APRT p.Cys153Arg Pathogenic 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-cys153 (accessed [today's date]).

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