Is P2RX4 p.Val64Phe (c.190G>T) pathogenic?

P2RX4 p.Val64Phe (c.190G>T) is classified Uncertain significance in P2RX4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-11). AlphaMissense: likely pathogenic (0.6446); Very rare (popmax 0.00133%, afr).

How common is P2RX4 p.Val64Phe (c.190G>T) in the general population?

P2RX4 p.Val64Phe (c.190G>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about P2RX4 p.Val64Phe (c.190G>T)?

AlphaMissense predicts likely pathogenic (score 0.6446) — an in-silico prediction, not a clinical call.

P2RX4 p.Val64Phe

c.190G>T · rs199523376 · VCV3207634

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6446 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6446	likely pathogenic
REVEL	0.456	indeterminate
SaProt	LLR -13.68	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 1.9, phastCons 0.96
Regional constraint	o/e 1.07	unconstrained · MANE · 19 kb · p 0.23 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,940 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000372% 6/1,614,104 alleles · very rare exomes 3/1,461,876 · genomes 3/152,228 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,940
European (non-Finnish)	0.000424%	236,007

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: P2RX4
Protein: p.Val64Phe
Coding: c.190G>T
MANE Select: NM_002560
dbSNP: rs199523376
Type: single nucleotide variant
Location: chr12:121217189 (GRCh38)
Gene constraint: LOEUF 1.08 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.43 · 4 PDB
Residue 64: a β-strand

Full P2RX4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

P2RX4 p.Val64Asp Uncertain significance ★ ⚠ same residue
P2RX4 p.Val64Ile Uncertain significance ★ ⚠ same residue
P2RX4 p.Val64Leu Uncertain significance ★ ⚠ same residue
P2RX4 c.978+8G>A Benign ★★ same type
P2RX4 p.Ala267Ser Uncertain significance ★ ⚠ same type
P2RX4 p.Ala349Thr Uncertain significance ★ ⚠ same type
P2RX4 p.Ala87Gly Uncertain significance ★ ⚠ same type
P2RX4 p.Ala87Val 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/p2rx4-p-val64phe (accessed [today's date]).

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