Is RNF125 p.Pro177= (c.531C>T) pathogenic?

RNF125 p.Pro177= (c.531C>T) is classified Likely benign in RNF125 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-26). Ultra-rare (popmax 0.0417%, amr); Associated with Tenorio syndrome.

What condition is associated with RNF125 p.Pro177= (c.531C>T)?

RNF125 p.Pro177= (c.531C>T) is associated with Tenorio syndrome (ClinVar).

How common is RNF125 p.Pro177= (c.531C>T) in the general population?

RNF125 p.Pro177= (c.531C>T) is ultra-rare (popmax 0.0417%, amr) (gnomAD).

RNF125 p.Pro177=

c.531C>T · VCV4812053

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0417%, amr)

Conditions

Tenorio syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.65	GERP -3.3, phastCons 0.007
Overall
CADD	3.974	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0417% Admixed American · 25/60,006 alleles

Filtering AF 0.0289% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0247%

Overall 0.00533% 86/1,613,460 alleles · ultra-rare exomes 63/1,461,192 · genomes 23/152,268 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0439%	2,277
Admixed Americangrpmax	0.0417%	2,400
African / African-American	0.00533%	18,758
East Asian	0.00446%	22,438
European (non-Finnish)	0.00339%	29,486
Remaining individualsnot grpmax-eligible	0.0032%	31,234

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: RNF125
Protein: p.Pro177=
Coding: c.531C>T
MANE Select: NM_017831
Type: single nucleotide variant
Location: chr18:32065928 (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

Tenorio syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RNF125 p.Arg220Gln Uncertain significance ★★ ⚠ same condition
RNF125 p.Glu224Gln Uncertain significance ★★ ⚠ same condition
RNF125 p.Ile123Thr Uncertain significance ★★ ⚠ same condition
RNF125 p.Pro128Thr Uncertain significance ★★ ⚠ same condition
RNF125 p.Ser163Leu Uncertain significance ★★ ⚠ same condition
RNF125 p.Ser59Pro Uncertain significance ★★ ⚠ same condition
RNF125 c.318+23T>G Benign ★★ same condition
RNF125 p.Arg165Gln Benign ★★ 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-pro177 (accessed [today's date]).

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