Is CTBP1 p.Pro372Arg (c.1115C>G) pathogenic?

CTBP1 p.Pro372Arg (c.1115C>G) is classified Likely benign in CTBP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-16). AlphaMissense: ambiguous (0.3437); Absent from gnomAD v4.1.

How common is CTBP1 p.Pro372Arg (c.1115C>G) in the general population?

CTBP1 p.Pro372Arg (c.1115C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTBP1 p.Pro372Arg (c.1115C>G)?

AlphaMissense predicts ambiguous (score 0.3437) — an in-silico prediction, not a clinical call.

CTBP1 p.Pro372Arg

c.1115C>G · VCV3910345

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3437 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.3437	ambiguous
REVEL	0.484	indeterminate
SaProt	LLR -9.60	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.5	GERP 0.63, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 16 kb · p 2.8e-17 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P383R vs ClinVar P372R) — verify the residue.

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: CTBP1
Protein: p.Pro372Arg
Coding: c.1115C>G
MANE Select: NM_001012614
Type: single nucleotide variant
Location: chr4:1212415 (GRCh38)
Gene constraint: LOEUF 0.533 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 84.08 · 11 PDB

Full CTBP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTBP1 p.Pro372= Likely benign ★ same residue
CTBP1 p.Arg331Trp Pathogenic ★★ ⚠ same type
CTBP1 c.-205C>G Uncertain significance ★★ ⚠ same type
CTBP1 p.Ala384Pro Uncertain significance ★★ ⚠ same type
CTBP1 p.Ala404Val Uncertain significance ★★ ⚠ same type
CTBP1 p.Arg173Cys Uncertain significance ★★ ⚠ same type
CTBP1 p.Gln137His Uncertain significance ★★ ⚠ same type
CTBP1 p.Gly399Ser 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/ctbp1-p-pro372arg (accessed [today's date]).

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