Is CUTC p.Arg48Pro (c.143G>C) pathogenic?

CUTC p.Arg48Pro (c.143G>C) is classified Uncertain significance in CUTC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-12). AlphaMissense: likely pathogenic (0.9956); Absent from gnomAD v4.1.

How common is CUTC p.Arg48Pro (c.143G>C) in the general population?

CUTC p.Arg48Pro (c.143G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CUTC p.Arg48Pro (c.143G>C)?

AlphaMissense predicts likely pathogenic (score 0.9956) — an in-silico prediction, not a clinical call.

CUTC p.Arg48Pro

c.143G>C · VCV4657729

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9956 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9956	likely pathogenic · top 1% in CUTC
REVEL	0.989	strongly pathogenic-leaning
SaProt	LLR -17.39	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 23 kb · p 0.12 · regional, not allelic
Overall
CADD	33.0	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

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: CUTC
Protein: p.Arg48Pro
Coding: c.143G>C
MANE Select: NM_015960
Type: single nucleotide variant
Location: chr10:99739719 (GRCh38)
Gene constraint: LOEUF 1.218 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.70 · 1 PDB
Residue 48: 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-arg48pro (accessed [today's date]).

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