Is APRT p.His54Asp (c.160C>G) pathogenic?

APRT p.His54Asp (c.160C>G) is classified Conflicting classifications of pathogenicity in APRT (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-07). AlphaMissense: likely pathogenic (0.5797); Ultra-rare (popmax 0.016%, nfe); Associated with adenine phosphoribosyltransferase deficiency.

What condition is associated with APRT p.His54Asp (c.160C>G)?

APRT p.His54Asp (c.160C>G) is associated with adenine phosphoribosyltransferase deficiency (ClinVar).

How common is APRT p.His54Asp (c.160C>G) in the general population?

APRT p.His54Asp (c.160C>G) is ultra-rare (popmax 0.016%, nfe) (gnomAD).

How is Adenine phosphoribosyltransferase deficiency inherited?

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

What do computational predictors say about APRT p.His54Asp (c.160C>G)?

AlphaMissense predicts likely pathogenic (score 0.5797) — an in-silico prediction, not a clinical call.

APRT p.His54Asp

c.160C>G · rs752977102 · VCV988039

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.5797 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

adenine phosphoribosyltransferase deficiency

Computational evidence

Protein change
AlphaMissense	0.5797	likely pathogenic
REVEL	0.4	indeterminate
SaProt	LLR -12.78	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	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	22.8	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 0.016% European (non-Finnish) · 188/1,175,284 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0134%

Overall 0.0125% 200/1,601,660 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.016%	6,252
African / African-American	0.0107%	9,337
Remaining individualsnot grpmax-eligible	0.00646%	15,482

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.His54Asp
Coding: c.160C>G
MANE Select: NM_000485
dbSNP: rs752977102
Type: single nucleotide variant
Location: chr16:88811577 (GRCh38)
Gene constraint: LOEUF 1.789 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.91 · 16 PDB
Residue 54: 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.His54= Benign/Likely benign ★★ 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-his54asp (accessed [today's date]).

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