Is P2RX2 p.Tyr55fs (c.162_172del) pathogenic?

P2RX2 p.Tyr55fs (c.162172del) is classified Uncertain significance in P2RX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-26). Very rare (popmax 0.00301%, sas).

How common is P2RX2 p.Tyr55fs (c.162_172del) in the general population?

P2RX2 p.Tyr55fs (c.162_172del) is very rare (popmax 0.00301%, sas) (gnomAD).

P2RX2 p.Tyr55fs

c.162_172del · VCV4774337

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00301%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.5	phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00301% South Asian · 1/33,258 alleles

Overall 7.84e-05% 1/1,275,062 alleles · very rare exomes 1/1,129,606 · genomes 0/145,456 · 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: P2RX2
Protein: p.Tyr55fs
Coding: c.162_172del
MANE Select: NM_170682
Type: Deletion
Location: chr12:132618977 (GRCh38)
Gene constraint: LOEUF 1.276 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.80 · 18 PDB

Full P2RX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

P2RX2 c.635+2_635+5del Uncertain significance ★★ same type
P2RX2 p.Glu71_Ser76del Uncertain significance ★★ same type
P2RX2 c.173+25_173+31del Likely benign ★★ same type
P2RX2 c.775-74_775-14del Benign/Likely benign ★★ same type
P2RX2 p.Ile441_Ser442insTer Benign/Likely benign ★★ same type
P2RX2 c.173+11_173+31del Uncertain significance ★ same type
P2RX2 c.314del Uncertain significance ★ same type
P2RX2 c.453_457+26del Uncertain significance ★ 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/p2rx2-p-tyr55fs (accessed [today's date]).

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