Is APRT p.Leu129= (c.385C>T) pathogenic?

APRT p.Leu129= (c.385C>T) is classified Likely benign in APRT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-05-12). Very rare (popmax 0.00223%, eas); Associated with adenine phosphoribosyltransferase deficiency.

What condition is associated with APRT p.Leu129= (c.385C>T)?

APRT p.Leu129= (c.385C>T) is associated with adenine phosphoribosyltransferase deficiency (ClinVar).

How common is APRT p.Leu129= (c.385C>T) in the general population?

APRT p.Leu129= (c.385C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Adenine phosphoribosyltransferase deficiency inherited?

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

APRT p.Leu129=

c.385C>T · rs376129456 · VCV1153854

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 5	GERP 0.42, phastCons 1
Overall
CADD	7.639	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,902 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000434% 7/1,613,154 alleles · very rare exomes 6/1,460,904 · genomes 1/152,250 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,902
European (non-Finnish)	0.000508%	196,675

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.Leu129=
Coding: c.385C>T
MANE Select: NM_000485
dbSNP: rs376129456
Type: single nucleotide variant
Location: chr16:88810085 (GRCh38)
Gene constraint: LOEUF 1.789 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.91 · 16 PDB
Residue 129: 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.Leu129Arg 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-leu129 (accessed [today's date]).

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