Is RNF216 p.Asp438= (c.1314C>T) pathogenic?

RNF216 p.Asp438= (c.1314C>T) is classified Likely benign in RNF216 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). Absent from gnomAD v4.1.

How common is RNF216 p.Asp438= (c.1314C>T) in the general population?

RNF216 p.Asp438= (c.1314C>T) is absent from gnomAD v4.1 (gnomAD).

RNF216 p.Asp438=

c.1314C>T · VCV4766134

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.2	GERP 0.48, phastCons 1
Overall
CADD	7.489	PHRED · no single calibrated threshold — expert panels disagree

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.Asp438=
Coding: c.1314C>T
MANE Select: NM_207111
Type: single nucleotide variant
Location: chr7:5729507 (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

Similar variants

RNF216 p.Asp438Asn Uncertain significance ★ ⚠ same residue
RNF216 p.Asp438Gly Uncertain significance ★ ⚠ same residue
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

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-asp438 (accessed [today's date]).

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