Is CTBP1 p.Pro292Ser (c.874C>T) pathogenic?

CTBP1 p.Pro292Ser (c.874C>T) is classified Uncertain significance in CTBP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-20). AlphaMissense: likely benign (0.1119); Ultra-rare (popmax 0.0128%, nfe).

How common is CTBP1 p.Pro292Ser (c.874C>T) in the general population?

CTBP1 p.Pro292Ser (c.874C>T) is ultra-rare (popmax 0.0128%, nfe) (gnomAD).

What do computational predictors say about CTBP1 p.Pro292Ser (c.874C>T)?

AlphaMissense predicts likely benign (score 0.1119) — an in-silico prediction, not a clinical call.

CTBP1 p.Pro292Ser

c.874C>T · rs369272423 · VCV2055726

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1119 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0128%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1119	likely benign
REVEL	0.515	indeterminate
SaProt	LLR -10.72	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 9.6	GERP -0.68, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 16 kb · p 2.8e-17 · regional, not allelic
Overall
CADD	25.2	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 P303S vs ClinVar P292S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0128% European (non-Finnish) · 151/1,179,894 alleles

Filtering AF 0.0111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0105%

Overall 0.00967% 156/1,612,980 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0128%	7,814
Remaining individualsnot grpmax-eligible	0.0064%	15,613
South Asian	0.0011%	91,088

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: CTBP1
Protein: p.Pro292Ser
Coding: c.874C>T
MANE Select: NM_001012614
dbSNP: rs369272423
Type: single nucleotide variant
Location: chr4:1213592 (GRCh38)
Gene constraint: LOEUF 0.533 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 84.08 · 11 PDB
Residue 292: the 'interaction with glis2 2' region

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

Similar variants

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
CTBP1 p.Ser426Asn 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-pro292ser (accessed [today's date]).

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