Is CTU2 p.Arg467Cys (c.1399C>T) pathogenic?

CTU2 p.Arg467Cys (c.1399C>T) is classified Benign/Likely benign in CTU2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-18). AlphaMissense: likely benign (0.2578); Rare (popmax 0.298%, mid); Associated with congenital anomaly of kidney and urinary tract.

What condition is associated with CTU2 p.Arg467Cys (c.1399C>T)?

CTU2 p.Arg467Cys (c.1399C>T) is associated with congenital anomaly of kidney and urinary tract (ClinVar).

How common is CTU2 p.Arg467Cys (c.1399C>T) in the general population?

CTU2 p.Arg467Cys (c.1399C>T) is rare (popmax 0.298%, mid) (gnomAD).

What do computational predictors say about CTU2 p.Arg467Cys (c.1399C>T)?

AlphaMissense predicts likely benign (score 0.2578) — an in-silico prediction, not a clinical call.

CTU2 p.Arg467Cys

c.1399C>T · rs139862860 · VCV1344612

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2578 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.298%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

congenital anomaly of kidney and urinary tract

Computational evidence

Protein change
AlphaMissense	0.2578	likely benign
REVEL	0.333	indeterminate
SaProt	LLR -11.68	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 1, phastCons 1
Regional constraint	o/e 1.61	unconstrained · MANE · 8,717 bp · p 1.9e-57 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.298% Middle Eastern · 18/6,048 alleles

Filtering AF 0.192% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.159%

Overall 0.101% 1,633/1,612,632 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.298%	336
Admixed American	0.138%	723
European (non-Finnish)	0.117%	852
Remaining individualsnot grpmax-eligible	0.0848%	1,179
South Asian	0.0582%	1,719
Ashkenazi Jewishnot grpmax-eligible	0.0541%	1,850
African / African-American	0.02%	5,003
East Asian	0.0111%	8,978
Finnishnot grpmax-eligible	0.00798%	12,534

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: CTU2
Protein: p.Arg467Cys
Coding: c.1399C>T
MANE Select: NM_001012759
dbSNP: rs139862860
Type: single nucleotide variant
Location: chr16:88714906 (GRCh38)
Gene constraint: LOEUF 1.535 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.27

Full CTU2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital anomaly of kidney and urinary tract — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CTU2 p.Arg467Gly Uncertain significance ★ ⚠ same residue
CTU2 p.Arg467His Uncertain significance ★ ⚠ same residue
CTU2 p.Gln165Glu Uncertain significance ★ ⚠ same condition
CTU2 c.1420-1G>A Likely pathogenic ★★ same type
CTU2 c.282+5G>A Pathogenic ★★ same type
CTU2 p.Gln243Ter Pathogenic/Likely pathogenic ★★ same type
CTU2 p.Thr291= Pathogenic ★★ same type
CTU2 p.Ala176Val 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/ctu2-p-arg467cys (accessed [today's date]).

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