Is BTBD16 p.Lys136Arg (c.407A>G) pathogenic?

BTBD16 p.Lys136Arg (c.407A>G) is classified Uncertain significance in BTBD16 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-10). AlphaMissense: likely benign (0.0734); Very rare (popmax 0.00668%, afr).

How common is BTBD16 p.Lys136Arg (c.407A>G) in the general population?

BTBD16 p.Lys136Arg (c.407A>G) is very rare (popmax 0.00668%, afr) (gnomAD).

What do computational predictors say about BTBD16 p.Lys136Arg (c.407A>G)?

AlphaMissense predicts likely benign (score 0.0734) — an in-silico prediction, not a clinical call.

BTBD16 p.Lys136Arg

c.407A>G · rs765965199 · VCV2512968

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0734 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0734	likely benign
REVEL	0.006	strongly benign-leaning
SaProt	LLR -6.73	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.013	GERP -1.4
Regional constraint	o/e 1.03	unconstrained · MANE · 63 kb · p 0.47 · regional, not allelic
Overall
CADD	11.88	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% African / African-American · 5/74,858 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00273% 44/1,613,714 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,972
European (non-Finnish)	0.00314%	31,890
East Asian	0.00223%	44,888
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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: BTBD16
Protein: p.Lys136Arg
Coding: c.407A>G
MANE Select: NM_144587
dbSNP: rs765965199
Type: single nucleotide variant
Location: chr10:122289930 (GRCh38)
Gene constraint: LOEUF 1.246 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.92

Full BTBD16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BTBD16 p.Ala113Val Uncertain significance ★ ⚠ same type
BTBD16 p.Ala161Thr Uncertain significance ★ ⚠ same type
BTBD16 p.Ala204Asp Uncertain significance ★ ⚠ same type
BTBD16 p.Ala362Thr Uncertain significance ★ ⚠ same type
BTBD16 p.Ala505Val Uncertain significance ★ ⚠ same type
BTBD16 p.Arg13Cys Uncertain significance ★ ⚠ same type
BTBD16 p.Arg197Ser Uncertain significance ★ ⚠ same type
BTBD16 p.Arg21Trp 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/btbd16-p-lys136arg (accessed [today's date]).

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