Is CUTC p.Arg168Cys (c.502C>T) pathogenic?

CUTC p.Arg168Cys (c.502C>T) is classified Uncertain significance in CUTC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-11). AlphaMissense: likely pathogenic (0.6121); Very rare (popmax 0.00659%, sas).

How common is CUTC p.Arg168Cys (c.502C>T) in the general population?

CUTC p.Arg168Cys (c.502C>T) is very rare (popmax 0.00659%, sas) (gnomAD).

What do computational predictors say about CUTC p.Arg168Cys (c.502C>T)?

AlphaMissense predicts likely pathogenic (score 0.6121) — an in-silico prediction, not a clinical call.

CUTC p.Arg168Cys

c.502C>T · VCV4236204

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6121 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6121	likely pathogenic
REVEL	0.868	moderately pathogenic-leaning
SaProt	LLR -13.51	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 23 kb · p 0.12 · regional, not allelic
Overall
CADD	28.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00659% South Asian · 6/91,084 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.00285% 46/1,614,008 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,181
African / African-American	0.00534%	18,732
European (non-Finnish)	0.0028%	35,757
East Asian	0.00223%	44,898
Admixed American	0.00167%	60,004
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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: CUTC
Protein: p.Arg168Cys
Coding: c.502C>T
MANE Select: NM_015960
Type: single nucleotide variant
Location: chr10:99747319 (GRCh38)
Gene constraint: LOEUF 1.218 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.70 · 1 PDB
Residue 168: a β-strand

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

Similar variants

COX15 c.-435C>T Benign ★★ same type
COX15 c.-472T>C Uncertain significance ★ same type
CUTC p.Ala13Pro Uncertain significance ★ ⚠ same type
CUTC p.Ala268Thr Uncertain significance ★ ⚠ same type
CUTC p.Ala46Asp Uncertain significance ★ ⚠ same type
CUTC p.Arg104Cys Uncertain significance ★ ⚠ same type
CUTC p.Arg104His Uncertain significance ★ ⚠ same type
CUTC p.Arg12Gly 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/cutc-p-arg168cys (accessed [today's date]).

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