Is RNF31 p.Arg389Ter (c.1165C>T) pathogenic?

RNF31 p.Arg389Ter (c.1165C>T) is classified Uncertain significance in RNF31 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-20). Very rare (popmax 8.48e-05%, nfe).

How common is RNF31 p.Arg389Ter (c.1165C>T) in the general population?

RNF31 p.Arg389Ter (c.1165C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

RNF31 p.Arg389Ter

c.1165C>T · rs2038245158 · VCV2008618

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 7 of 21
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.26	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 3.3	GERP 1.8, phastCons 1
Overall
CADD	37.0	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 8.48e-05% European (non-Finnish) · 1/1,179,258 alleles

Overall 0.000186% 3/1,612,194 alleles · very rare exomes 3/1,459,890 · genomes 0/152,304 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00313%	31,998
European (non-Finnish)grpmax	8.48e-05%	1,179,258

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg389Ter
Coding: c.1165C>T
MANE Select: NM_017999
dbSNP: rs2038245158
Type: single nucleotide variant
Location: chr14:24150416 (GRCh38)
Gene constraint: LOEUF 0.37 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.39 · 36 PDB
Residue 389: the 'polyubiquitin-binding' region

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

Similar variants

RNF31 p.Arg389Gln Uncertain significance ★ ⚠ same residue
RNF31 p.Ala251Val Uncertain significance ★★ ⚠ same type
RNF31 p.Ala350Gly Uncertain significance ★★ ⚠ same type
RNF31 p.Ala45Val Uncertain significance ★★ ⚠ same type
RNF31 p.Ala501Thr Uncertain significance ★★ ⚠ same type
RNF31 p.Ala503Ser Uncertain significance ★★ ⚠ same type
RNF31 p.Ala503Thr Uncertain significance ★★ ⚠ same type
RNF31 p.Ala539Val 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-arg389ter (accessed [today's date]).

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