Is RNF216 p.Pro51Arg (c.152C>G) pathogenic?

RNF216 p.Pro51Arg (c.152C>G) is classified Likely benign in RNF216 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-11). AlphaMissense: likely benign (0.0903); Rare (popmax 0.167%, eas).

How common is RNF216 p.Pro51Arg (c.152C>G) in the general population?

RNF216 p.Pro51Arg (c.152C>G) is rare (popmax 0.167%, eas) (gnomAD).

What do computational predictors say about RNF216 p.Pro51Arg (c.152C>G)?

AlphaMissense predicts likely benign (score 0.0903) — an in-silico prediction, not a clinical call.

RNF216 p.Pro51Arg

c.152C>G · rs200061775 · VCV759643

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0903 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.167%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0903	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -7.00	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 12	GERP 4.2, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 138 kb · p 2.8e-09 · regional, not allelic
Overall
CADD	20.1	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 0.167% East Asian · 75/44,844 alleles

Filtering AF 0.137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.126%

Overall 0.00478% 77/1,612,474 alleles · rare exomes 65/1,460,208 · genomes 12/152,266 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.167%	598
Remaining individualsnot grpmax-eligible	0.0016%	62,466
African / African-American	0.00133%	74,996

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: RNF216
Protein: p.Pro51Arg
Coding: c.152C>G
MANE Select: NM_207111
dbSNP: rs200061775
Type: single nucleotide variant
Location: chr7:5752895 (GRCh38)
Gene constraint: LOEUF 0.819 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.91 · 4 PDB
Residue 51: the 'disordered' region

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

Similar variants

RNF216 p.Trp229Ter Pathogenic/Likely pathogenic ★★ same type
RNF216 p.Ala314Pro Uncertain significance ★★ ⚠ same type
RNF216 p.Ala588Thr Uncertain significance ★★ ⚠ same type
RNF216 p.Ala652Val Uncertain significance ★★ ⚠ same type
RNF216 p.Arg262His Uncertain significance ★★ ⚠ same type
RNF216 p.Arg391Thr Uncertain significance ★★ ⚠ same type
RNF216 p.Arg426His Uncertain significance ★★ ⚠ same type
RNF216 p.Arg525Gln 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/rnf216-p-pro51arg (accessed [today's date]).

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