Is CRPPA p.Pro70Arg (c.209C>G) pathogenic?

CRPPA p.Pro70Arg (c.209C>G) is classified Uncertain significance in CRPPA (ClinVar, Single submitter, 1 submitter; last evaluated 2015-10-22). AlphaMissense: likely benign (0.0816); Absent from gnomAD v4.1.

How common is CRPPA p.Pro70Arg (c.209C>G) in the general population?

CRPPA p.Pro70Arg (c.209C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CRPPA p.Pro70Arg (c.209C>G)?

AlphaMissense predicts likely benign (score 0.0816) — an in-silico prediction, not a clinical call.

CRPPA p.Pro70Arg

c.209C>G · rs886042746 · VCV283943

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0816 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0816	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -7.17	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 0.62	GERP 0.7, phastCons 0.095
Regional constraint	o/e 1.14	unconstrained · MANE · 330 kb · p 0.001 · regional, not allelic
Overall
CADD	14.16	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: CRPPA
Protein: p.Pro70Arg
Coding: c.209C>G
MANE Select: NM_001101426
dbSNP: rs886042746
Type: single nucleotide variant
Location: chr7:16421114 (GRCh38)
Gene constraint: LOEUF 1.462 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.63 · 1 PDB

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

Similar variants

CRPPA c.1120-1G>T Pathogenic ★★ same type
CRPPA c.258-1G>C Pathogenic/Likely pathogenic ★★ same type
CRPPA c.835+2T>C Pathogenic/Likely pathogenic ★★ same type
CRPPA p.Arg184Ter Pathogenic ★★ same type
CRPPA p.Arg205Cys Likely pathogenic ★★ same type
CRPPA p.Arg268Ter Pathogenic ★★ same type
CRPPA p.Gln215Ter Pathogenic/Likely pathogenic ★★ same type
CRPPA c.1026+5G>C 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/crppa-p-pro70arg (accessed [today's date]).

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