Is CTBP1 p.Ala112= (c.336G>A) pathogenic?

CTBP1 p.Ala112= (c.336G>A) is classified Uncertain significance in CTBP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-03-11). Very rare (popmax 0.00822%, afr); Associated with hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome.

What condition is associated with CTBP1 p.Ala112= (c.336G>A)?

CTBP1 p.Ala112= (c.336G>A) is associated with hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome (ClinVar).

How common is CTBP1 p.Ala112= (c.336G>A) in the general population?

CTBP1 p.Ala112= (c.336G>A) is very rare (popmax 0.00822%, afr) (gnomAD).

CTBP1 p.Ala112=

c.336G>A · rs965475865 · VCV2440595

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00822%, afr)

Conditions

hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -14	GERP -3.4
Overall
CADD	1.536	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00822% African / African-American · 6/73,022 alleles

Filtering AF 0.00355% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00243%

Overall 0.00117% 18/1,543,062 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00822%	12,170
East Asian	0.00244%	40,916
Admixed American	0.00196%	50,972
Remaining individualsnot grpmax-eligible	0.00167%	59,998
European (non-Finnish)	0.000785%	127,400

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.Ala112=
Coding: c.336G>A
MANE Select: NM_001012614
dbSNP: rs965475865
Type: single nucleotide variant
Location: chr4:1225538 (GRCh38)
Gene constraint: LOEUF 0.533 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 84.08 · 11 PDB
Residue 112: an α-helix

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

Disease context

hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CTBP1 p.Arg331Trp Pathogenic ★★ ⚠ same condition
CTBP1 p.Arg173Cys Uncertain significance ★★ ⚠ same condition
CTBP1 p.Gln137His Uncertain significance ★★ ⚠ same condition
CTBP1 p.Gly399Ser Uncertain significance ★★ ⚠ same condition
CTBP1 p.Val359Met Uncertain significance ★★ ⚠ same condition
CTBP1 p.Val416Ile Uncertain significance ★★ ⚠ same condition
CTBP1 p.Arg162= Benign/Likely benign ★★ same condition
CTBP1 p.Ala347Ser Uncertain significance ★ ⚠ same condition

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-ala112 (accessed [today's date]).

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