Is P2RX2 p.Ile62= (c.186C>T) pathogenic?

P2RX2 p.Ile62= (c.186C>T) is classified Benign in P2RX2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-28). Low-frequency (popmax 1.62%, nfe).

How common is P2RX2 p.Ile62= (c.186C>T) in the general population?

P2RX2 p.Ile62= (c.186C>T) is low-frequency (popmax 1.62%, nfe) (gnomAD).

P2RX2 p.Ile62=

c.186C>T · rs75585377 · VCV226983

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.62%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.117	moderately benign-leaning
Splicing
SpliceAI	Δ0.29	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -0.81	phastCons 0.005
Overall
CADD	15.54	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.62% European (non-Finnish) · 19,075/1,179,346 alleles

Filtering AF 1.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.59%

Overall 1.45% 23,360/1,612,196 alleles · low-frequency exomes 21,786/1,460,106 · genomes 1,574/152,090 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	2.05%	49
European (non-Finnish)grpmax	1.62%	62
South Asian	1.61%	62
Middle Eastern	1.5%	67
Remaining individualsnot grpmax-eligible	1.31%	76
Admixed American	1.05%	96
Finnishnot grpmax-eligible	0.745%	134
African / African-American	0.271%	369
East Asian	0.0067%	14,929

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile62=
Coding: c.186C>T
MANE Select: NM_170682
dbSNP: rs75585377
Type: single nucleotide variant
Location: chr12:132619451 (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.174-1G>A Uncertain significance ★★ same type
P2RX2 p.Arg218His Uncertain significance ★★ ⚠ same type
P2RX2 p.Arg286Gln Uncertain significance ★★ ⚠ same type
P2RX2 p.Arg302Thr Uncertain significance ★★ ⚠ same type
P2RX2 p.Arg315Cys Uncertain significance ★★ ⚠ same type
P2RX2 p.Arg315His Uncertain significance ★★ ⚠ same type
P2RX2 p.Arg324Cys Uncertain significance ★★ ⚠ same type
P2RX2 p.Asp180Asn 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-ile62 (accessed [today's date]).

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