Is APRT p.Asn137= (c.411C>T) pathogenic?

APRT p.Asn137= (c.411C>T) is classified Conflicting classifications of pathogenicity in APRT (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-03-07). Ultra-rare (popmax 0.0783%, amr); Associated with adenine phosphoribosyltransferase deficiency.

What condition is associated with APRT p.Asn137= (c.411C>T)?

APRT p.Asn137= (c.411C>T) is associated with adenine phosphoribosyltransferase deficiency (ClinVar).

How common is APRT p.Asn137= (c.411C>T) in the general population?

APRT p.Asn137= (c.411C>T) is ultra-rare (popmax 0.0783%, amr) (gnomAD).

How is Adenine phosphoribosyltransferase deficiency inherited?

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

APRT p.Asn137=

c.411C>T · rs142472789 · VCV884719

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0783%, amr)

Conditions

adenine phosphoribosyltransferase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -20	GERP -3.2
Overall
CADD	0.004	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0783% Admixed American · 47/59,994 alleles

Filtering AF 0.0604% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0542%

Overall 0.00968% 156/1,611,938 alleles · ultra-rare exomes 128/1,459,698 · genomes 28/152,240 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.172%	580
Admixed Americangrpmax	0.0783%	1,276
Middle Eastern	0.0164%	6,082
Remaining individualsnot grpmax-eligible	0.016%	6,247
East Asian	0.00445%	22,450
European (non-Finnish)	0.00364%	27,439
African / African-American	0.00267%	37,469

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asn137=
Coding: c.411C>T
MANE Select: NM_000485
dbSNP: rs142472789
Type: single nucleotide variant
Location: chr16:88809830 (GRCh38)
Gene constraint: LOEUF 1.789 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.91 · 16 PDB
Residue 137: an α-helix

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.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
APRT p.Met1Val 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-asn137 (accessed [today's date]).

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