Is RNF13 p.Pro73Gln (c.218C>A) pathogenic?

RNF13 p.Pro73Gln (c.218C>A) is classified Uncertain significance in RNF13 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-10). AlphaMissense: likely pathogenic (0.9977); Absent from gnomAD v4.1.

How common is RNF13 p.Pro73Gln (c.218C>A) in the general population?

RNF13 p.Pro73Gln (c.218C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RNF13 p.Pro73Gln (c.218C>A)?

AlphaMissense predicts likely pathogenic (score 0.9977) — an in-silico prediction, not a clinical call.

RNF13 p.Pro73Gln

c.218C>A · rs2108442079 · VCV1393934

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9977 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9977	likely pathogenic · top 10% in RNF13
REVEL	0.459	indeterminate
SaProt	LLR -14.31	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 115 kb · p 0.00025 · regional, not allelic
Overall
CADD	27.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: RNF13
Protein: p.Pro73Gln
Coding: c.218C>A
MANE Select: NM_183381
dbSNP: rs2108442079
Type: single nucleotide variant
Location: chr3:149872051 (GRCh38)
Gene constraint: LOEUF 0.813 · pLI 0.59 (gnomAD)
Structure: AlphaFold pLDDT 74.65 · 2 PDB
Residue 73: the pa domain

Full RNF13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RNF13 p.Ala378Val Uncertain significance ★★ ⚠ same type
RNF13 p.Arg212Thr Uncertain significance ★★ ⚠ same type
RNF13 p.Arg215Lys Uncertain significance ★★ ⚠ same type
RNF13 p.Arg219His Uncertain significance ★★ ⚠ same type
RNF13 p.Arg98Gly Uncertain significance ★★ ⚠ same type
RNF13 p.Asn346Ser Uncertain significance ★★ ⚠ same type
RNF13 p.Glu181Gln Uncertain significance ★★ ⚠ same type
RNF13 p.Ile137Val 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/rnf13-p-pro73gln (accessed [today's date]).

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