Is BTBD10 p.Asp174Val (c.521A>T) pathogenic?

BTBD10 p.Asp174Val (c.521A>T) is classified Uncertain significance in BTBD10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: likely pathogenic (0.9993); Absent from gnomAD v4.1.

How common is BTBD10 p.Asp174Val (c.521A>T) in the general population?

BTBD10 p.Asp174Val (c.521A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BTBD10 p.Asp174Val (c.521A>T)?

AlphaMissense predicts likely pathogenic (score 0.9993) — an in-silico prediction, not a clinical call.

BTBD10 p.Asp174Val

c.521A>T · rs2499714297 · VCV3135370

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9993 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9993	likely pathogenic · top 9% in BTBD10
REVEL	0.784	moderately pathogenic-leaning
SaProt	LLR -12.17	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.34 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.1	GERP 1.3, phastCons 1
Regional constraint	o/e 0.53	unconstrained · MANE · 14 kb · p 7.4e-10 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BTBD10
Protein: p.Asp174Val
Coding: c.521A>T
MANE Select: NM_032320
dbSNP: rs2499714297
Type: single nucleotide variant
Location: chr11:13419523 (GRCh38)
Gene constraint: LOEUF 0.587 · pLI 0.63 (gnomAD)
Structure: AlphaFold pLDDT 69.79
Residue 174: the btb domain; 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-asp174val (accessed [today's date]).

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