Is BTBD8 p.Lys344= (c.1032G>A) pathogenic?

BTBD8 p.Lys344= (c.1032G>A) is classified Likely benign in BTBD8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-01). Rare (popmax 0.359%, nfe).

How common is BTBD8 p.Lys344= (c.1032G>A) in the general population?

BTBD8 p.Lys344= (c.1032G>A) is rare (popmax 0.359%, nfe) (gnomAD).

BTBD8 p.Lys344=

c.1032G>A · rs139460683 · VCV2638929

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.359%, 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 -0.27, phastCons 1
Overall
CADD	6.506	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.359% European (non-Finnish) · 4,232/1,178,210 alleles

Filtering AF 0.35% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.346%

Overall 0.292% 4,691/1,607,862 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.768%	130
European (non-Finnish)grpmax	0.359%	278
Remaining individualsnot grpmax-eligible	0.196%	511
Middle Eastern	0.149%	670
South Asian	0.146%	685
Admixed American	0.119%	837
Finnishnot grpmax-eligible	0.0877%	1,140
Ashkenazi Jewishnot grpmax-eligible	0.0647%	1,546
African / African-American	0.0602%	1,661
East Asian	0.00223%	44,770

Amish 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: BTBD8
Protein: p.Lys344=
Coding: c.1032G>A
MANE Select: NM_001376131
dbSNP: rs139460683
Type: single nucleotide variant
Location: chr1:92147696 (GRCh38)
Gene constraint: LOEUF 0.753 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.10

Full BTBD8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BTBD8 p.Ala347Ser Uncertain significance ★ ⚠ same type
BTBD8 p.Ala356Thr Uncertain significance ★ ⚠ same type
BTBD8 p.Ala74Val Uncertain significance ★ ⚠ same type
BTBD8 p.Arg79Gly Uncertain significance ★ ⚠ same type
BTBD8 p.Asn181Ser Uncertain significance ★ ⚠ same type
BTBD8 p.Asp170His Uncertain significance ★ ⚠ same type
BTBD8 p.Asp182Val Uncertain significance ★ ⚠ same type
BTBD8 p.Asp209Asn 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/btbd8-p-lys344 (accessed [today's date]).

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