Is BTBD2 p.Ala54Ser (c.160G>T) pathogenic?

BTBD2 p.Ala54Ser (c.160G>T) is classified Uncertain significance in BTBD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-03). AlphaMissense: likely benign (0.0844); Common (popmax 20.5%, eas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about BTBD2 p.Ala54Ser (c.160G>T)?

AlphaMissense predicts likely benign (score 0.0844) — an in-silico prediction, not a clinical call.

BTBD2 p.Ala54Ser

Q: How common is BTBD2 p.Ala54Ser (c.160G>T) in the general population?

BTBD2 p.Ala54Ser (c.160G>T) is common (popmax 20.5%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.160G>T · rs1213128407 · VCV2515344

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0844 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 20.5%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0844	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -8.22	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 -0.83	GERP -0.66, phastCons 0.001
Regional constraint	o/e 1.01	unconstrained · MANE · 18 kb · p 0.86 · regional, not allelic
Overall
CADD	8.228	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 20.5% East Asian · 9/44 alleles

Filtering AF 10.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.97%

Overall 0.0853% 11/12,896 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	20.5%	5
Remaining individualsnot grpmax-eligible	0.568%	176

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: BTBD2
Protein: p.Ala54Ser
Coding: c.160G>T
MANE Select: NM_017797
dbSNP: rs1213128407
Type: single nucleotide variant
Location: chr19:2015544 (GRCh38)
Gene constraint: LOEUF 0.635 · pLI 0.28 (gnomAD)
Structure: AlphaFold pLDDT 84.82 · 1 PDB
Residue 54: the 'disordered' region

Full BTBD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BTBD2 p.Ala201Ser Uncertain significance ★ ⚠ same type
BTBD2 p.Ala201Val Uncertain significance ★ ⚠ same type
BTBD2 p.Ala33Gly Uncertain significance ★ ⚠ same type
BTBD2 p.Ala37Val Uncertain significance ★ ⚠ same type
BTBD2 p.Ala3Thr Uncertain significance ★ ⚠ same type
BTBD2 p.Ala41Glu Uncertain significance ★ ⚠ same type
BTBD2 p.Ala42Ser Uncertain significance ★ ⚠ same type
BTBD2 p.Ala446Val 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/btbd2-p-ala54ser (accessed [today's date]).

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