Is RNPEP p.Pro606Arg (c.1817C>G) pathogenic?

RNPEP p.Pro606Arg (c.1817C>G) is classified Uncertain significance in RNPEP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-21). AlphaMissense: likely pathogenic (0.8299); Very rare (popmax 0.004%, afr).

How common is RNPEP p.Pro606Arg (c.1817C>G) in the general population?

RNPEP p.Pro606Arg (c.1817C>G) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about RNPEP p.Pro606Arg (c.1817C>G)?

AlphaMissense predicts likely pathogenic (score 0.8299) — an in-silico prediction, not a clinical call.

RNPEP p.Pro606Arg

c.1817C>G · VCV3434642

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8299 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8299	likely pathogenic
REVEL	0.704	pathogenic-leaning
SaProt	LLR -7.64	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 23 kb · p 0.025 · regional, not allelic
Overall
CADD	25.6	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 0.004% African / African-American · 3/74,916 alleles

Filtering AF 0.00307% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00275%

Overall 0.00316% 51/1,614,066 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,972
European (non-Finnish)	0.00398%	25,107
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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: RNPEP
Protein: p.Pro606Arg
Coding: c.1817C>G
Type: single nucleotide variant
Location: chr1:202005580 (GRCh38)

Full RNPEP 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/rnpep-p-pro606arg (accessed [today's date]).

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