Is RNF216 p.Pro160= (c.480G>A) pathogenic?

RNF216 p.Pro160= (c.480G>A) is classified Likely benign in RNF216 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-01). Very rare (popmax 0.00329%, sas); Associated with RNF216-related disorder.

What condition is associated with RNF216 p.Pro160= (c.480G>A)?

RNF216 p.Pro160= (c.480G>A) is associated with RNF216-related disorder (ClinVar).

How common is RNF216 p.Pro160= (c.480G>A) in the general population?

RNF216 p.Pro160= (c.480G>A) is very rare (popmax 0.00329%, sas) (gnomAD).

RNF216 p.Pro160=

c.480G>A · VCV3351961

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Conditions

RNF216-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.15	GERP 2.1, phastCons 0.74
Overall
CADD	8.506	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,090 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000805% 13/1,614,030 alleles · very rare exomes 10/1,461,886 · genomes 3/152,144 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,363
African / African-American	0.00267%	37,446
European (non-Finnish)	0.000678%	147,505

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.Pro160=
Coding: c.480G>A
MANE Select: NM_207111
Type: single nucleotide variant
Location: chr7:5741537 (GRCh38)
Gene constraint: LOEUF 0.819 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.91 · 4 PDB
Residue 160: the 'disordered' region

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

Disease context

RNF216-related disorder

Similar variants

RNF216 p.Pro160Gln Uncertain significance ★ ⚠ same residue
RNF216 p.Pro160Leu Uncertain significance ★ ⚠ same residue
RNF216 c.67+2T>A Likely pathogenic ★ same condition
RNF216 p.Arg751Cys Likely pathogenic ★ same condition
RNF216 p.Pro242Leu Uncertain significance ★ ⚠ same condition
RNF216 p.Tyr539Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
RNF216 p.Ala860= Likely benign same condition
RNF216 p.Lys70fs Likely pathogenic ★ 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-pro160 (accessed [today's date]).

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