Is CTBP2 p.Ser326= (c.978T>C) pathogenic?

CTBP2 p.Ser326= (c.978T>C) is classified Likely benign in CTBP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-01). Ultra-rare (popmax 0.0112%, nfe).

How common is CTBP2 p.Ser326= (c.978T>C) in the general population?

CTBP2 p.Ser326= (c.978T>C) is ultra-rare (popmax 0.0112%, nfe) (gnomAD).

CTBP2 p.Ser326=

c.978T>C · rs141956363 · VCV2640947

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, nfe)

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 -0.23	GERP -4.8, phastCons 0.002
Overall
CADD	5.976	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0112% European (non-Finnish) · 132/1,174,864 alleles

Filtering AF 0.00965% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00908%

Overall 0.00852% 137/1,607,560 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0112%	8,901
Remaining individualsnot grpmax-eligible	0.00644%	15,519
African / African-American	0.00134%	74,790

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.Ser326=
Coding: c.978T>C
MANE Select: NM_001329
dbSNP: rs141956363
Type: single nucleotide variant
Location: chr10:124993263 (GRCh38)
Gene constraint: LOEUF 0.522 · pLI 0.82 (gnomAD)
Structure: AlphaFold pLDDT 83.67 · 5 PDB

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
CTBP2 p.Pro309= Benign ★★ same type
ZRANB1 p.Arg669Trp Uncertain significance ★ ⚠ same type
ZRANB1 p.Arg670Trp Uncertain significance ★ ⚠ same type
ZRANB1 p.Arg688Gln 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-ser326 (accessed [today's date]).

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