Is PRCD p.Arg22Pro (c.65G>C) pathogenic?

PRCD p.Arg22Pro (c.65G>C) is classified Uncertain significance in PRCD (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-27). AlphaMissense: ambiguous (0.5592); Very rare (popmax 9.16e-05%, nfe).

How common is PRCD p.Arg22Pro (c.65G>C) in the general population?

PRCD p.Arg22Pro (c.65G>C) is very rare (popmax 9.16e-05%, nfe) (gnomAD).

What do computational predictors say about PRCD p.Arg22Pro (c.65G>C)?

AlphaMissense predicts ambiguous (score 0.5592) — an in-silico prediction, not a clinical call.

PRCD p.Arg22Pro

c.65G>C · VCV4937132

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5592 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 9.16e-05%, nfe)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.5592	ambiguous
REVEL	0.317	indeterminate
SaProt	LLR -9.53	tolerated
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.4	GERP 0.52, phastCons 0.99
Regional constraint	o/e 0.84	unconstrained · MANE · 2,429 bp · p 0.19 · regional, not allelic
Overall
CADD	24.9	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 9.16e-05% European (non-Finnish) · 1/1,091,766 alleles

Overall 6.81e-05% 1/1,467,376 alleles · very rare exomes 1/1,325,076 · genomes 0/142,300 · 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: PRCD
Protein: p.Arg22Pro
Coding: c.65G>C
MANE Select: NM_001077620
Type: single nucleotide variant
Location: chr17:76540206 (GRCh38)

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

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/prcd-p-arg22pro (accessed [today's date]).

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