Is CTBP2 p.Pro309= (c.927G>A) pathogenic?

CTBP2 p.Pro309= (c.927G>A) is classified Benign in CTBP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-12-26). Common (popmax 5.78%, afr) — too common for a highly-penetrant pathogenic allele.

CTBP2 p.Pro309=

Q: How common is CTBP2 p.Pro309= (c.927G>A) in the general population?

CTBP2 p.Pro309= (c.927G>A) is common (popmax 5.78%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.927G>A · rs76804352 · VCV779348

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.78%, afr) — too common for a highly-penetrant pathogenic allele

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 -3.7	GERP -4.8
Overall
CADD	3.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.78% African / African-American · 4,331/74,896 alleles

Filtering AF 5.64% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.58%

Overall 0.326% 5,247/1,608,626 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.78%	17
Admixed American	0.539%	186
Remaining individualsnot grpmax-eligible	0.433%	231
Middle Eastern	0.215%	464
European (non-Finnish)	0.0249%	4,012
South Asian	0.0154%	6,487
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,382

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: CTBP2
Protein: p.Pro309=
Coding: c.927G>A
MANE Select: NM_001329
dbSNP: rs76804352
Type: single nucleotide variant
Location: chr10:124993314 (GRCh38)
Gene constraint: LOEUF 0.522 · pLI 0.82 (gnomAD)
Structure: AlphaFold pLDDT 83.67 · 5 PDB
Residue 309: a turn

Full CTBP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTBP2 c.58+11873C>T Benign ★★ same type
CTBP2 c.58+11963C>T Benign ★★ same type
CTBP2 c.58+12441C>T Benign ★★ same type
CTBP2 c.58+12475A>C Benign ★★ same type
ZRANB1 p.Arg669Trp Uncertain significance ★ ⚠ same type
ZRANB1 p.Arg670Trp Uncertain significance ★ ⚠ same type
ZRANB1 p.Arg688Gln Uncertain significance ★ ⚠ same type
ZRANB1 p.Arg691Trp 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/ctbp2-p-pro309 (accessed [today's date]).

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