Is BTBD10 p.Ile245Val (c.733A>G) pathogenic?

BTBD10 p.Ile245Val (c.733A>G) is classified Uncertain significance in BTBD10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-28). AlphaMissense: likely benign (0.269); Very rare (popmax 0.0077%, sas).

How common is BTBD10 p.Ile245Val (c.733A>G) in the general population?

BTBD10 p.Ile245Val (c.733A>G) is very rare (popmax 0.0077%, sas) (gnomAD).

What do computational predictors say about BTBD10 p.Ile245Val (c.733A>G)?

AlphaMissense predicts likely benign (score 0.269) — an in-silico prediction, not a clinical call.

BTBD10 p.Ile245Val

c.733A>G · VCV3482723

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.269 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0077%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.269	likely benign
REVEL	0.292	indeterminate
SaProt	LLR -5.23	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.2, phastCons 1
Regional constraint	o/e 0.53	unconstrained · MANE · 14 kb · p 7.4e-10 · regional, not allelic
Overall
CADD	21.6	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 0.0077% South Asian · 7/90,940 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00261% 42/1,611,776 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0077%	12,991
Admixed American	0.00501%	19,972
African / African-American	0.00401%	24,963
Finnishnot grpmax-eligible	0.00313%	31,916
European (non-Finnish)	0.00221%	45,329
Remaining individualsnot grpmax-eligible	0.0016%	62,380

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.Ile245Val
Coding: c.733A>G
MANE Select: NM_032320
Type: single nucleotide variant
Location: chr11:13413605 (GRCh38)
Gene constraint: LOEUF 0.587 · pLI 0.63 (gnomAD)
Structure: AlphaFold pLDDT 69.79
Residue 245: the 'interaction with akt family members' 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-ile245val (accessed [today's date]).

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