Is RNF13 p.Pro227Ser (c.679C>T) pathogenic?

RNF13 p.Pro227Ser (c.679C>T) is classified Uncertain significance in RNF13 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-01). AlphaMissense: likely pathogenic (0.8939); No allele count reported in gnomAD v4.1 (AN 1,409,462).

How common is RNF13 p.Pro227Ser (c.679C>T) in the general population?

RNF13 p.Pro227Ser (c.679C>T) is no allele count reported in gnomAD v4.1 (AN 1,409,462) (gnomAD).

What do computational predictors say about RNF13 p.Pro227Ser (c.679C>T)?

AlphaMissense predicts likely pathogenic (score 0.8939) — an in-silico prediction, not a clinical call.

RNF13 p.Pro227Ser

c.679C>T · VCV3771381

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8939 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,409,462)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8939	likely pathogenic
REVEL	0.425	indeterminate
SaProt	LLR -8.42	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 115 kb · p 0.00025 · regional, not allelic
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,409,462). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RNF13
Protein: p.Pro227Ser
Coding: c.679C>T
MANE Select: NM_183381
Type: single nucleotide variant
Location: chr3:149921206 (GRCh38)
Gene constraint: LOEUF 0.813 · pLI 0.59 (gnomAD)
Structure: AlphaFold pLDDT 74.65 · 2 PDB

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

Similar variants

RNF13 p.Pro227Arg Likely benign ★ ⚠ same residue
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

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-pro227ser (accessed [today's date]).

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