Is RNF10 p.Pro491Arg (c.1472C>G) pathogenic?

RNF10 p.Pro491Arg (c.1472C>G) is classified Uncertain significance in RNF10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-01). AlphaMissense: likely benign (0.0864); Very rare (popmax 0.00834%, amr).

How common is RNF10 p.Pro491Arg (c.1472C>G) in the general population?

RNF10 p.Pro491Arg (c.1472C>G) is very rare (popmax 0.00834%, amr) (gnomAD).

What do computational predictors say about RNF10 p.Pro491Arg (c.1472C>G)?

AlphaMissense predicts likely benign (score 0.0864) — an in-silico prediction, not a clinical call.

RNF10 p.Pro491Arg

c.1472C>G · VCV3946323

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0864 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00834%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0864	likely benign
REVEL	0.251	benign-leaning
SaProt	LLR -7.31	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP 0.91, phastCons 0.007
Regional constraint	o/e 0.93	unconstrained · MANE · 42 kb · p 0.035 · regional, not allelic
Overall
CADD	18.01	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00834% Admixed American · 5/59,966 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000434% 7/1,613,606 alleles · very rare exomes 5/1,461,462 · genomes 2/152,144 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00834%	11,993
European (non-Finnish)	0.00017%	589,908

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: RNF10
Protein: p.Pro491Arg
Coding: c.1472C>G
MANE Select: NM_014868
Type: single nucleotide variant
Location: chr12:120563564 (GRCh38)
Gene constraint: LOEUF 0.519 · pLI 0.76 (gnomAD)
Structure: AlphaFold pLDDT 65.67

Full RNF10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RNF10 p.Pro491Leu Uncertain significance ★ ⚠ same residue
RNF10 p.Gly387Arg Benign ★★ same type
RNF10 p.Ala130Thr Uncertain significance ★ ⚠ same type
RNF10 p.Ala409Val Uncertain significance ★ ⚠ same type
RNF10 p.Ala723Thr Uncertain significance ★ ⚠ same type
RNF10 p.Ala771Pro Uncertain significance ★ ⚠ same type
RNF10 p.Arg378Trp Uncertain significance ★ ⚠ same type
RNF10 p.Arg499Cys 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/rnf10-p-pro491arg (accessed [today's date]).

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