Is RNF13 p.Pro186Ser (c.556C>T) pathogenic?

RNF13 p.Pro186Ser (c.556C>T) is classified Uncertain significance in RNF13 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-03). AlphaMissense: likely pathogenic (0.9939); Very rare (popmax 0.00402%, afr).

How common is RNF13 p.Pro186Ser (c.556C>T) in the general population?

RNF13 p.Pro186Ser (c.556C>T) is very rare (popmax 0.00402%, afr) (gnomAD).

What do computational predictors say about RNF13 p.Pro186Ser (c.556C>T)?

AlphaMissense predicts likely pathogenic (score 0.9939) — an in-silico prediction, not a clinical call.

RNF13 p.Pro186Ser

c.556C>T · rs146054064 · VCV1917331

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9939 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00402%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9939	likely pathogenic
REVEL	0.345	indeterminate
SaProt	LLR -13.97	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 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 115 kb · p 0.00025 · regional, not allelic
Overall
CADD	23.4	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

Grpmax group 0.00402% African / African-American · 3/74,598 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000496%

Overall 0.000187% 3/1,600,360 alleles · very rare exomes 1/1,448,238 · genomes 2/152,122 · 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: RNF13
Protein: p.Pro186Ser
Coding: c.556C>T
MANE Select: NM_183381
dbSNP: rs146054064
Type: single nucleotide variant
Location: chr3:149912033 (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.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-pro186ser (accessed [today's date]).

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