Is APRT c.80+2T>C pathogenic?

APRT c.80+2T>C is classified Pathogenic in APRT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-29). Very rare (popmax 0.00943%, amr).

How common is APRT c.80+2T>C in the general population?

APRT c.80+2T>C is very rare (popmax 0.00943%, amr) (gnomAD).

APRT c.80+2T>C

VCV4698132

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00943%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +2	canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone
SpliceAI	Δ0.62	donor loss, 2 bp away · masked 0 · deltas
Pangolin	Δ0.49	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 8.7	GERP 1.1, phastCons 1
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00943% Admixed American · 5/53,028 alleles

Filtering AF 0.0037% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0024%

Overall 0.000511% 8/1,565,092 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00943%	10,606
European (non-Finnish)	0.000259%	385,661

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
Coding: c.80+2T>C
MANE Select: NM_000485
Type: single nucleotide variant
Location: chr16:88811818 (GRCh38)
Gene constraint: LOEUF 1.789 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.91 · 16 PDB

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

Similar variants

APRT p.Arg67Gln Likely pathogenic ★★ same type
APRT p.Arg67Ter Pathogenic ★★ same type
APRT p.Arg87Ter Pathogenic ★★ same type
APRT p.Asp65Val Pathogenic ★★ same type
APRT p.Gly133Arg Likely pathogenic ★★ same type
APRT p.Gly63Asp Likely pathogenic ★★ same type
APRT p.Met1Ile Pathogenic ★★ same type
APRT p.Met1Val Pathogenic ★★ same type

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-c-80-plus-2t-c (accessed [today's date]).

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