Is RNF125 p.Leu175Ser (c.524T>C) pathogenic?

RNF125 p.Leu175Ser (c.524T>C) is classified Uncertain significance in RNF125 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-26). AlphaMissense: likely benign (0.1259); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with RNF125 p.Leu175Ser (c.524T>C)?

RNF125 p.Leu175Ser (c.524T>C) is associated with Inborn genetic diseases (ClinVar).

How common is RNF125 p.Leu175Ser (c.524T>C) in the general population?

RNF125 p.Leu175Ser (c.524T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RNF125 p.Leu175Ser (c.524T>C)?

AlphaMissense predicts likely benign (score 0.1259) — an in-silico prediction, not a clinical call.

RNF125 p.Leu175Ser

c.524T>C · rs2510930847 · VCV3155006

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1259 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1259	likely benign
REVEL	0.172	moderately benign-leaning
SaProt	LLR -4.89	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 6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 50 kb · p 0.09 · regional, not allelic
Overall
CADD	20.3	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

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: RNF125
Protein: p.Leu175Ser
Coding: c.524T>C
MANE Select: NM_017831
dbSNP: rs2510930847
Type: single nucleotide variant
Location: chr18:32065921 (GRCh38)
Gene constraint: LOEUF 1.071 · pLI 0.20 (gnomAD)
Structure: AlphaFold pLDDT 77.90 · 3 PDB

Full RNF125 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RNF125 p.Arg220Gln Uncertain significance ★★ ⚠ same condition
RNF125 p.Ile123Thr Uncertain significance ★★ ⚠ same condition
RNF125 p.Pro128Thr Uncertain significance ★★ ⚠ same condition
RNF125 p.Ser59Pro Uncertain significance ★★ ⚠ same condition
RNF125 p.Asn67Ile Uncertain significance ★ ⚠ same condition
RNF125 p.Asp178Asn Conflicting classifications of pathogenicity ★ ⚠ same condition
RNF125 p.Cys173Tyr Uncertain significance ★ ⚠ same condition
RNF125 p.Gln130Arg Uncertain significance ★ ⚠ same condition

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/rnf125-p-leu175ser (accessed [today's date]).

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