Is APRT p.Glu78Lys (c.232G>A) pathogenic?

APRT p.Glu78Lys (c.232G>A) is classified Uncertain significance in APRT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-05). AlphaMissense: ambiguous (0.3425); Very rare (popmax 0.00102%, nfe); Associated with Inborn genetic diseases.

What condition is associated with APRT p.Glu78Lys (c.232G>A)?

APRT p.Glu78Lys (c.232G>A) is associated with Inborn genetic diseases (ClinVar).

How common is APRT p.Glu78Lys (c.232G>A) in the general population?

APRT p.Glu78Lys (c.232G>A) is very rare (popmax 0.00102%, nfe) (gnomAD).

What do computational predictors say about APRT p.Glu78Lys (c.232G>A)?

AlphaMissense predicts ambiguous (score 0.3425) — an in-silico prediction, not a clinical call.

APRT p.Glu78Lys

c.232G>A · rs1182857791 · VCV3128095

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3425 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3425	ambiguous
REVEL	0.451	indeterminate
SaProt	LLR -12.37	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.6, phastCons 1
Regional constraint	o/e 1.26	unconstrained · MANE · 2,198 bp · p 5.8e-05 · regional, not allelic
Overall
CADD	21.2	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 0.00102% European (non-Finnish) · 12/1,179,932 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000744% 12/1,612,186 alleles · very rare exomes 8/1,459,986 · genomes 4/152,200 · joint denominator

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.Glu78Lys
Coding: c.232G>A
MANE Select: NM_000485
dbSNP: rs1182857791
Type: single nucleotide variant
Location: chr16:88810512 (GRCh38)
Gene constraint: LOEUF 1.789 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.91 · 16 PDB
Residue 78: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

APRT p.Ala138Thr Uncertain significance ★★ ⚠ same condition
APRT p.Arg89Trp Uncertain significance ★★ ⚠ same condition
APRT p.Asp59Asn Uncertain significance ★★ ⚠ same condition
APRT p.Ile61Val Uncertain significance ★★ ⚠ same condition
APRT p.Leu129Arg Uncertain significance ★★ ⚠ same condition
APRT p.Pro17Ala Uncertain significance ★★ ⚠ same condition
APRT p.Ala116Val Uncertain significance ★ ⚠ same condition
APRT p.Asp3Gly Uncertain significance ★ ⚠ 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-glu78lys (accessed [today's date]).

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