Is CTBP1 p.Ser283= (c.849G>A) pathogenic?

CTBP1 p.Ser283= (c.849G>A) is classified Likely benign in CTBP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-01). Very rare (popmax 0.0042%, afr).

How common is CTBP1 p.Ser283= (c.849G>A) in the general population?

CTBP1 p.Ser283= (c.849G>A) is very rare (popmax 0.0042%, afr) (gnomAD).

CTBP1 p.Ser283=

c.849G>A · rs764484563 · VCV1591789

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0042%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.061	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -3.1
Overall
CADD	8.661	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0042% African / African-American · 3/71,492 alleles

Filtering AF 0.0014% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00117%

Overall 0.00236% 37/1,565,490 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00663%	15,090
African / African-Americangrpmax	0.0042%	23,831
South Asian	0.00356%	28,055
East Asian	0.00241%	41,498
European (non-Finnish)	0.00207%	48,423
Admixed American	0.00201%	49,684
Finnishnot grpmax-eligible	0.00162%	61,546

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser283=
Coding: c.849G>A
MANE Select: NM_001012614
dbSNP: rs764484563
Type: single nucleotide variant
Location: chr4:1214354 (GRCh38)
Gene constraint: LOEUF 0.533 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 84.08 · 11 PDB
Residue 283: a β-strand

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

Similar variants

CTBP1 p.Ser283Leu 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-ser283 (accessed [today's date]).

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