Is CTBP1 p.Pro7Gln (c.20C>A) pathogenic?

CTBP1 p.Pro7Gln (c.20C>A) is classified Uncertain significance in CTBP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-10). AlphaMissense: likely benign (0.1443); Very rare (popmax 0.00135%, afr).

How common is CTBP1 p.Pro7Gln (c.20C>A) in the general population?

CTBP1 p.Pro7Gln (c.20C>A) is very rare (popmax 0.00135%, afr) (gnomAD).

What do computational predictors say about CTBP1 p.Pro7Gln (c.20C>A)?

AlphaMissense predicts likely benign (score 0.1443) — an in-silico prediction, not a clinical call.

CTBP1 p.Pro7Gln

c.20C>A · rs1731790714 · VCV1949699

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1443 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00135%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1443	likely benign
REVEL	0.249	benign-leaning
SaProt	LLR -8.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	GERP -0.95, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 3,026 bp · p 0.69 · regional, not allelic
Overall
CADD	21.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 P18Q vs ClinVar P7Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00135% African / African-American · 1/73,988 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000191% 3/1,573,588 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00135%	73,988
European (non-Finnish)	0.000173%	577,955

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.Pro7Gln
Coding: c.20C>A
MANE Select: NM_001012614
dbSNP: rs1731790714
Type: single nucleotide variant
Location: chr4:1238325 (GRCh38)
Gene constraint: LOEUF 0.533 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 84.08 · 11 PDB
Residue 7: the 'interaction with glis2 1' region

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

Similar variants

CTBP1 p.Pro7Leu Uncertain significance ★ ⚠ 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-pro7gln (accessed [today's date]).

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