Is BTBD10 p.Ser130Arg (c.388A>C) pathogenic?

BTBD10 p.Ser130Arg (c.388A>C) is classified Uncertain significance in BTBD10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-21). AlphaMissense: ambiguous (0.535); Very rare (popmax 0.00533%, afr).

How common is BTBD10 p.Ser130Arg (c.388A>C) in the general population?

BTBD10 p.Ser130Arg (c.388A>C) is very rare (popmax 0.00533%, afr) (gnomAD).

What do computational predictors say about BTBD10 p.Ser130Arg (c.388A>C)?

AlphaMissense predicts ambiguous (score 0.535) — an in-silico prediction, not a clinical call.

BTBD10 p.Ser130Arg

c.388A>C · rs772752682 · VCV3135369

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.535 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00533%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.535	ambiguous
REVEL	0.033	moderately benign-leaning
SaProt	LLR -6.25	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 0.22, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 2,174 bp · p 0.38 · regional, not allelic
Overall
CADD	21.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00533% African / African-American · 4/75,068 alleles

Filtering AF 0.00174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000342% 5/1,461,836 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00533%	18,767
Remaining individualsnot grpmax-eligible	0.0016%	62,510

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.Ser130Arg
Coding: c.388A>C
MANE Select: NM_032320
dbSNP: rs772752682
Type: single nucleotide variant
Location: chr11:13419656 (GRCh38)
Gene constraint: LOEUF 0.587 · pLI 0.63 (gnomAD)
Structure: AlphaFold pLDDT 69.79
Residue 130: 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-ser130arg (accessed [today's date]).

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