Is P2RX6 p.Arg34Ser (c.102G>C) pathogenic?

P2RX6 p.Arg34Ser (c.102G>C) is classified Uncertain significance in P2RX6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-26). AlphaMissense: ambiguous (0.4563); Very rare (popmax 8.63e-05%, nfe).

How common is P2RX6 p.Arg34Ser (c.102G>C) in the general population?

P2RX6 p.Arg34Ser (c.102G>C) is very rare (popmax 8.63e-05%, nfe) (gnomAD).

What do computational predictors say about P2RX6 p.Arg34Ser (c.102G>C)?

AlphaMissense predicts ambiguous (score 0.4563) — an in-silico prediction, not a clinical call.

P2RX6 p.Arg34Ser

c.102G>C · VCV3413014

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4563 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.63e-05%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4563	ambiguous
REVEL	0.186	benign-leaning
SaProt	LLR -8.03	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 0.24, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 11 kb · p 0.81 · regional, not allelic
Overall
CADD	24.4	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 8.63e-05% European (non-Finnish) · 1/1,158,308 alleles

Overall 6.43e-05% 1/1,554,330 alleles · very rare exomes 1/1,402,022 · genomes 0/152,308 · 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: P2RX6
Protein: p.Arg34Ser
Coding: c.102G>C
MANE Select: NM_005446
Type: single nucleotide variant
Location: chr22:21015276 (GRCh38)
Gene constraint: LOEUF 1.531 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.89

Full P2RX6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

P2RX6 p.Tyr52Cys Uncertain significance ★★ ⚠ same type
P2RX6 p.Ala382Thr Uncertain significance ★ ⚠ same type
P2RX6 p.Ala400Ser Uncertain significance ★ ⚠ same type
P2RX6 p.Ala40Thr Uncertain significance ★ ⚠ same type
P2RX6 p.Ala60Ser Uncertain significance ★ ⚠ same type
P2RX6 p.Ala8Gly Uncertain significance ★ ⚠ same type
P2RX6 p.Ala98Asp Uncertain significance ★ ⚠ same type
P2RX6 p.Arg169Gly 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/p2rx6-p-arg34ser (accessed [today's date]).

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