Is CTBP1 p.Phe42Ser (c.125T>C) pathogenic?

CTBP1 p.Phe42Ser (c.125T>C) is classified Uncertain significance in CTBP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-08-31). AlphaMissense: likely pathogenic (0.9999); Absent from gnomAD v4.1.

How common is CTBP1 p.Phe42Ser (c.125T>C) in the general population?

CTBP1 p.Phe42Ser (c.125T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTBP1 p.Phe42Ser (c.125T>C)?

AlphaMissense predicts likely pathogenic (score 0.9999) — an in-silico prediction, not a clinical call.

CTBP1 p.Phe42Ser

c.125T>C · rs1553848965 · VCV451754

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic · top 2% in CTBP1
REVEL	0.457	indeterminate
SaProt	LLR -14.46	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.21	constrained · MANE · 9,968 bp · p 6.2e-10 · regional, not allelic
Overall
CADD	29.0	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM F53S vs ClinVar F42S) — 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.Phe42Ser
Coding: c.125T>C
MANE Select: NM_001012614
dbSNP: rs1553848965
Type: single nucleotide variant
Location: chr4:1238220 (GRCh38)
Gene constraint: LOEUF 0.533 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 84.08 · 11 PDB
Residue 42: the 'interaction with glis2 1' region; an α-helix

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

Similar variants

CTBP1 p.Phe42del Likely pathogenic ★ 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-phe42ser (accessed [today's date]).

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