Is BTBD8 p.Ala347Ser (c.1039G>T) pathogenic?

BTBD8 p.Ala347Ser (c.1039G>T) is classified Uncertain significance in BTBD8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-25). AlphaMissense: likely benign (0.1096); Absent from gnomAD v4.1.

How common is BTBD8 p.Ala347Ser (c.1039G>T) in the general population?

BTBD8 p.Ala347Ser (c.1039G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BTBD8 p.Ala347Ser (c.1039G>T)?

AlphaMissense predicts likely benign (score 0.1096) — an in-silico prediction, not a clinical call.

BTBD8 p.Ala347Ser

c.1039G>T · VCV3825956

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1096 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1096	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -5.37	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 6.4	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 101 kb · p 0.071 · regional, not allelic
Overall
CADD	21.1	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

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: BTBD8
Protein: p.Ala347Ser
Coding: c.1039G>T
MANE Select: NM_001376131
Type: single nucleotide variant
Location: chr1:92147703 (GRCh38)
Gene constraint: LOEUF 0.753 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.10

Full BTBD8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BTBD8 p.Ala356Thr Uncertain significance ★ ⚠ same type
BTBD8 p.Ala74Val Uncertain significance ★ ⚠ same type
BTBD8 p.Arg79Gly Uncertain significance ★ ⚠ same type
BTBD8 p.Asn181Ser Uncertain significance ★ ⚠ same type
BTBD8 p.Asp170His Uncertain significance ★ ⚠ same type
BTBD8 p.Asp182Val Uncertain significance ★ ⚠ same type
BTBD8 p.Asp209Asn Uncertain significance ★ ⚠ same type
BTBD8 p.Cys238Tyr 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/btbd8-p-ala347ser (accessed [today's date]).

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