Is BTBD10 p.Arg20Trp (c.58C>T) pathogenic?

BTBD10 p.Arg20Trp (c.58C>T) is classified Uncertain significance in BTBD10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-18). AlphaMissense: likely benign (0.1061); Ultra-rare (popmax 0.0584%, amr).

How common is BTBD10 p.Arg20Trp (c.58C>T) in the general population?

BTBD10 p.Arg20Trp (c.58C>T) is ultra-rare (popmax 0.0584%, amr) (gnomAD).

What do computational predictors say about BTBD10 p.Arg20Trp (c.58C>T)?

AlphaMissense predicts likely benign (score 0.1061) — an in-silico prediction, not a clinical call.

BTBD10 p.Arg20Trp

c.58C>T · rs553554748 · VCV2382508

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1061 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0584%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1061	likely benign
REVEL	0.305	indeterminate
SaProt	LLR -9.41	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.24	donor loss, 43 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 9.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 23 kb · p 0.86 · regional, not allelic
Overall
CADD	25.7	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 0.0584% Admixed American · 35/59,946 alleles

Filtering AF 0.0431% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0378%

Overall 0.00415% 67/1,613,054 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0584%	1,713
Remaining individualsnot grpmax-eligible	0.0176%	5,677
Middle Eastern	0.0165%	6,046
South Asian	0.00549%	18,208
East Asian	0.00446%	22,422
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,552
European (non-Finnish)	0.00102%	98,279

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: BTBD10
Protein: p.Arg20Trp
Coding: c.58C>T
MANE Select: NM_032320
dbSNP: rs553554748
Type: single nucleotide variant
Location: chr11:13445067 (GRCh38)
Gene constraint: LOEUF 0.587 · pLI 0.63 (gnomAD)
Structure: AlphaFold pLDDT 69.79
Residue 20: the 'disordered' region

Full BTBD10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BTBD10 p.Arg114Cys Uncertain significance ★ ⚠ same type
BTBD10 p.Arg238Cys Uncertain significance ★ ⚠ same type
BTBD10 p.Arg238His Uncertain significance ★ ⚠ same type
BTBD10 p.Arg306Trp Uncertain significance ★ ⚠ same type
BTBD10 p.Arg4Trp Uncertain significance ★ ⚠ same type
BTBD10 p.Arg65Gln Uncertain significance ★ ⚠ same type
BTBD10 p.Arg72Gln Uncertain significance ★ ⚠ same type
BTBD10 p.Asp174Val 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/btbd10-p-arg20trp (accessed [today's date]).

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