Is CTBP1 p.Ala263Val (c.788C>T) pathogenic?

CTBP1 p.Ala263Val (c.788C>T) is classified Uncertain significance in CTBP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-27). AlphaMissense: ambiguous (0.5304); Very rare (popmax 7.01e-05%).

How common is CTBP1 p.Ala263Val (c.788C>T) in the general population?

CTBP1 p.Ala263Val (c.788C>T) is very rare (popmax 7.01e-05%) (gnomAD).

What do computational predictors say about CTBP1 p.Ala263Val (c.788C>T)?

AlphaMissense predicts ambiguous (score 0.5304) — an in-silico prediction, not a clinical call.

CTBP1 p.Ala263Val

c.788C>T · rs777093230 · VCV1196693

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5304 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 7.01e-05%)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5304	ambiguous
REVEL	0.749	pathogenic-leaning
SaProt	LLR -13.04	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.62, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 16 kb · p 2.8e-17 · regional, not allelic
Overall
CADD	29.4	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 A274V vs ClinVar A263V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.01e-05%

Overall 7.01e-05% 1/1,426,678 alleles · very rare

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.Ala263Val
Coding: c.788C>T
MANE Select: NM_001012614
dbSNP: rs777093230
Type: single nucleotide variant
Location: chr4:1214415 (GRCh38)
Gene constraint: LOEUF 0.533 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 84.08 · 11 PDB
Residue 263: a β-strand

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

Similar variants

CTBP1 p.Ala263= 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-ala263val (accessed [today's date]).

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