Is BTBD2 p.Pro65= (c.195C>T) pathogenic?

BTBD2 p.Pro65= (c.195C>T) is classified Likely benign in BTBD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-01). Very rare (popmax 0.00852%, nfe).

How common is BTBD2 p.Pro65= (c.195C>T) in the general population?

BTBD2 p.Pro65= (c.195C>T) is very rare (popmax 0.00852%, nfe) (gnomAD).

BTBD2 p.Pro65=

c.195C>T · rs1419976629 · VCV2648958

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00852%, 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 -0.81	GERP -1.4
Overall
CADD	13.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00852% European (non-Finnish) · 71/833,500 alleles

Filtering AF 0.00688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00632%

Overall 0.0073% 72/986,096 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00852%	11,739
Remaining individualsnot grpmax-eligible	0.00335%	29,894

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: BTBD2
Protein: p.Pro65=
Coding: c.195C>T
MANE Select: NM_017797
dbSNP: rs1419976629
Type: single nucleotide variant
Location: chr19:2015509 (GRCh38)
Gene constraint: LOEUF 0.635 · pLI 0.28 (gnomAD)
Structure: AlphaFold pLDDT 84.82 · 1 PDB
Residue 65: the 'disordered' region

Full BTBD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BTBD2 p.Ala201Ser Uncertain significance ★ ⚠ same type
BTBD2 p.Ala201Val Uncertain significance ★ ⚠ same type
BTBD2 p.Ala33Gly Uncertain significance ★ ⚠ same type
BTBD2 p.Ala37Val Uncertain significance ★ ⚠ same type
BTBD2 p.Ala3Thr Uncertain significance ★ ⚠ same type
BTBD2 p.Ala41Glu Uncertain significance ★ ⚠ same type
BTBD2 p.Ala42Ser Uncertain significance ★ ⚠ same type
BTBD2 p.Ala446Val 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/btbd2-p-pro65 (accessed [today's date]).

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