Is BTBD9 p.Ile364= (c.1092A>C) pathogenic?

BTBD9 p.Ile364= (c.1092A>C) is classified Likely benign in BTBD9 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-29). Very rare (popmax 0.00263%, nfe).

How common is BTBD9 p.Ile364= (c.1092A>C) in the general population?

BTBD9 p.Ile364= (c.1092A>C) is very rare (popmax 0.00263%, nfe) (gnomAD).

BTBD9 p.Ile364=

c.1092A>C · rs750281932 · VCV737264

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00263%, 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 1.3	GERP -5.1, phastCons 1
Overall
CADD	6.373	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00263% European (non-Finnish) · 31/1,179,318 alleles

Filtering AF 0.00188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00164%

Overall 0.00192% 31/1,610,572 alleles · very rare

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: BTBD9
Protein: p.Ile364=
Coding: c.1092A>C
MANE Select: NM_001099272
dbSNP: rs750281932
Type: single nucleotide variant
Location: chr6:38577662 (GRCh38)
Gene constraint: LOEUF 0.959 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.71

Full BTBD9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BTBD9 p.Ala100Val Uncertain significance ★ ⚠ same type
BTBD9 p.Ala28Thr Uncertain significance ★ ⚠ same type
BTBD9 p.Ala476Thr Uncertain significance ★ ⚠ same type
BTBD9 p.Ala590Val Uncertain significance ★ ⚠ same type
BTBD9 p.Ala76Val Uncertain significance ★ ⚠ same type
BTBD9 p.Arg257Gly Uncertain significance ★ ⚠ same type
BTBD9 p.Arg319His Uncertain significance ★ ⚠ same type
BTBD9 p.Arg336Gly 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/btbd9-p-ile364 (accessed [today's date]).

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