Is RNF10 p.Pro671Ser (c.2011C>T) pathogenic?

RNF10 p.Pro671Ser (c.2011C>T) is classified Uncertain significance in RNF10 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-27). AlphaMissense: likely benign (0.0617); Very rare (popmax 0.00222%, sas).

How common is RNF10 p.Pro671Ser (c.2011C>T) in the general population?

RNF10 p.Pro671Ser (c.2011C>T) is very rare (popmax 0.00222%, sas) (gnomAD).

What do computational predictors say about RNF10 p.Pro671Ser (c.2011C>T)?

AlphaMissense predicts likely benign (score 0.0617) — an in-silico prediction, not a clinical call.

RNF10 p.Pro671Ser

c.2011C>T · rs761359348 · VCV2313924

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0617 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00222%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0617	likely benign
REVEL	0.273	benign-leaning
SaProt	LLR -5.68	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 0.59	GERP 0.079, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 42 kb · p 0.035 · regional, not allelic
Overall
CADD	13.3	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 0.00222% South Asian · 2/90,042 alleles

Filtering AF 0.000369% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000138%

Overall 0.000186% 3/1,609,240 alleles · very rare exomes 3/1,456,966 · genomes 0/152,274 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00222%	45,021
European (non-Finnish)	8.48e-05%	1,178,834

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.Pro671Ser
Coding: c.2011C>T
MANE Select: NM_014868
dbSNP: rs761359348
Type: single nucleotide variant
Location: chr12:120566950 (GRCh38)
Gene constraint: LOEUF 0.519 · pLI 0.76 (gnomAD)
Structure: AlphaFold pLDDT 65.67
Residue 671: the 'disordered' region

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

Similar variants

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
RNF10 p.Arg525His 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-pro671ser (accessed [today's date]).

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