Is BTBD10 p.His58Arg (c.173A>G) pathogenic?

BTBD10 p.His58Arg (c.173A>G) is classified Uncertain significance in BTBD10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-09). AlphaMissense: likely benign (0.0966); Very rare (popmax 0.00549%, sas).

How common is BTBD10 p.His58Arg (c.173A>G) in the general population?

BTBD10 p.His58Arg (c.173A>G) is very rare (popmax 0.00549%, sas) (gnomAD).

What do computational predictors say about BTBD10 p.His58Arg (c.173A>G)?

AlphaMissense predicts likely benign (score 0.0966) — an in-silico prediction, not a clinical call.

BTBD10 p.His58Arg

c.173A>G · VCV3993416

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0966 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0966	likely benign
REVEL	0.09	moderately benign-leaning
SaProt	LLR -3.87	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 1.2	GERP 1.1, phastCons 0.94
Regional constraint	o/e 0.98	unconstrained · MANE · 23 kb · p 0.86 · regional, not allelic
Overall
CADD	14.85	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 0.00549% South Asian · 5/91,088 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000547% 8/1,461,802 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,218
Remaining individualsnot grpmax-eligible	0.0016%	62,508
European (non-Finnish)	0.000169%	589,998

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.His58Arg
Coding: c.173A>G
MANE Select: NM_032320
Type: single nucleotide variant
Location: chr11:13421767 (GRCh38)
Gene constraint: LOEUF 0.587 · pLI 0.63 (gnomAD)
Structure: AlphaFold pLDDT 69.79
Residue 58: 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.Arg20Trp 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

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-his58arg (accessed [today's date]).

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