Is RPRD2 p.Pro565Arg (c.1694C>G) pathogenic?

RPRD2 p.Pro565Arg (c.1694C>G) is classified Uncertain significance in RPRD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-08). AlphaMissense: likely benign (0.278); Absent from gnomAD v4.1.

How common is RPRD2 p.Pro565Arg (c.1694C>G) in the general population?

RPRD2 p.Pro565Arg (c.1694C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RPRD2 p.Pro565Arg (c.1694C>G)?

AlphaMissense predicts likely benign (score 0.278) — an in-silico prediction, not a clinical call.

RPRD2 p.Pro565Arg

c.1694C>G · rs767748023 · VCV2305715

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.278 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.278	likely benign
REVEL	0.29	benign-leaning
SaProt	LLR -7.93	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 54 kb · p 1.7e-14 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RPRD2
Protein: p.Pro565Arg
Coding: c.1694C>G
MANE Select: NM_015203
dbSNP: rs767748023
Type: single nucleotide variant
Location: chr1:150470642 (GRCh38)
Gene constraint: LOEUF 0.145 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 48.32 · 3 PDB
Residue 565: the 'disordered' region

Full RPRD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RPRD2 p.Glu195= Benign ★★ same type
RPRD2 p.Ala1083Ser Uncertain significance ★ ⚠ same type
RPRD2 p.Ala1145Pro Uncertain significance ★ ⚠ same type
RPRD2 p.Ala1149Val Uncertain significance ★ ⚠ same type
RPRD2 p.Ala1165Val Uncertain significance ★ ⚠ same type
RPRD2 p.Ala1251Thr Uncertain significance ★ ⚠ same type
RPRD2 p.Ala140Val Uncertain significance ★ ⚠ same type
RPRD2 p.Ala442Pro 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/rprd2-p-pro565arg (accessed [today's date]).

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