Is RNF216 p.Pro31Arg (c.92C>G) pathogenic?

RNF216 p.Pro31Arg (c.92C>G) is classified Uncertain significance in RNF216 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-04). AlphaMissense: likely benign (0.1753); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with RNF216 p.Pro31Arg (c.92C>G)?

RNF216 p.Pro31Arg (c.92C>G) is associated with Inborn genetic diseases (ClinVar).

How common is RNF216 p.Pro31Arg (c.92C>G) in the general population?

RNF216 p.Pro31Arg (c.92C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RNF216 p.Pro31Arg (c.92C>G)?

AlphaMissense predicts likely benign (score 0.1753) — an in-silico prediction, not a clinical call.

RNF216 p.Pro31Arg

c.92C>G · rs781594576 · VCV3155326

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1753 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1753	likely benign
REVEL	0.161	moderately benign-leaning
SaProt	LLR -9.55	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 9.8	GERP 4, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 138 kb · p 2.8e-09 · regional, not allelic
Overall
CADD	24.3	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: RNF216
Protein: p.Pro31Arg
Coding: c.92C>G
MANE Select: NM_207111
dbSNP: rs781594576
Type: single nucleotide variant
Location: chr7:5752955 (GRCh38)
Gene constraint: LOEUF 0.819 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.91 · 4 PDB

Full RNF216 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RNF216 p.Ala314Pro Uncertain significance ★★ ⚠ same condition
RNF216 p.Ala588Thr Uncertain significance ★★ ⚠ same condition
RNF216 p.Arg426His Uncertain significance ★★ ⚠ same condition
RNF216 p.Arg525Gln Uncertain significance ★★ ⚠ same condition
RNF216 p.Arg686Gln Uncertain significance ★★ ⚠ same condition
RNF216 p.Arg895Gln Uncertain significance ★★ ⚠ same condition
RNF216 p.Arg920Gln Uncertain significance ★★ ⚠ same condition
RNF216 p.Asn324Ser Uncertain significance ★★ ⚠ same condition

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/rnf216-p-pro31arg (accessed [today's date]).

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