Is RNF31 p.Asp24fs (c.70del) pathogenic?

RNF31 p.Asp24fs (c.70del) is classified Uncertain significance in RNF31 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-06). Very rare (popmax 0.000258%, nfe).

How common is RNF31 p.Asp24fs (c.70del) in the general population?

RNF31 p.Asp24fs (c.70del) is very rare (popmax 0.000258%, nfe) (gnomAD).

RNF31 p.Asp24fs

c.70del · rs2038191896 · VCV2855714

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000258%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 1 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.2	GERP 0.58, phastCons 1
Overall
CADD	21.7	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000258% European (non-Finnish) · 3/1,163,948 alleles

Filtering AF 6.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00019% 3/1,575,246 alleles · very rare exomes 1/1,423,176 · genomes 2/152,070 · joint denominator

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: RNF31
Protein: p.Asp24fs
Coding: c.70del
MANE Select: NM_017999
dbSNP: rs2038191896
Type: Deletion
Location: chr14:24147766 (GRCh38)
Gene constraint: LOEUF 0.37 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.39 · 36 PDB
Residue 24: the 'polyubiquitin-binding' region

Full RNF31 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RNF31 p.Asp24Gly Uncertain significance ★ ⚠ same residue
RNF31 c.193-2_196del Uncertain significance ★ same type
RNF31 c.2403+6_2403+9del Uncertain significance ★ same type
RNF31 c.340-2del Uncertain significance ★ same type
RNF31 p.Arg749_Asp751del Uncertain significance ★ same type
RNF31 p.Asn672_Tyr673insTer Uncertain significance ★ same type
RNF31 p.Cys415fs Uncertain significance ★ same type
RNF31 p.Gly474_Pro476del 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/rnf31-p-asp24fs (accessed [today's date]).

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