Is BTBD6 p.Phe394= (c.1182C>T) pathogenic?

BTBD6 p.Phe394= (c.1182C>T) is classified Benign in BTBD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-01). Low-frequency (popmax 2.23%, mid).

How common is BTBD6 p.Phe394= (c.1182C>T) in the general population?

BTBD6 p.Phe394= (c.1182C>T) is low-frequency (popmax 2.23%, mid) (gnomAD).

BTBD6 p.Phe394=

c.1182C>T · rs61740085 · VCV2644912

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 2.23%, mid)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4	GERP 2.2, phastCons 1
Overall
CADD	13.13	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.23% Middle Eastern · 135/6,062 alleles

Filtering AF 1.92% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.81%

Overall 1.18% 18,968/1,613,016 alleles · low-frequency exomes 17,567/1,460,658 · genomes 1,401/152,358 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	2.51%	40
Middle Easterngrpmax	2.23%	45
European (non-Finnish)	1.33%	75
Remaining individualsnot grpmax-eligible	1.18%	85
South Asian	0.955%	105
Admixed American	0.885%	113
African / African-American	0.248%	404
Finnishnot grpmax-eligible	0.127%	786
East Asian	0.0111%	8,977

Ashkenazi Jewish 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: BTBD6
Protein: p.Phe394=
Coding: c.1182C>T
MANE Select: NM_001387567
dbSNP: rs61740085
Type: single nucleotide variant
Location: chr14:105250237 (GRCh38)

Full BTBD6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/btbd6-p-phe394 (accessed [today's date]).

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