Is BTBD7 p.Ala983Pro (c.2947G>C) pathogenic?

BTBD7 p.Ala983Pro (c.2947G>C) is classified Uncertain significance in BTBD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-25). AlphaMissense: likely benign (0.0765); Ultra-rare (popmax 0.0602%, eas).

How common is BTBD7 p.Ala983Pro (c.2947G>C) in the general population?

BTBD7 p.Ala983Pro (c.2947G>C) is ultra-rare (popmax 0.0602%, eas) (gnomAD).

What do computational predictors say about BTBD7 p.Ala983Pro (c.2947G>C)?

AlphaMissense predicts likely benign (score 0.0765) — an in-silico prediction, not a clinical call.

BTBD7 p.Ala983Pro

c.2947G>C · rs147201730 · VCV3135449

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0765 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0602%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0765	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -5.84	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 2.2	GERP 0.95, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 4,007 bp · p 0.18 · regional, not allelic
Overall
CADD	18.61	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 0.0602% East Asian · 27/44,880 alleles

Filtering AF 0.0424% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0365%

Overall 0.00285% 46/1,614,080 alleles · ultra-rare exomes 43/1,461,894 · genomes 3/152,186 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0602%	1,662
South Asian	0.0143%	7,005
Admixed American	0.00167%	60,008
Remaining individualsnot grpmax-eligible	0.0016%	62,508
European (non-Finnish)	0.000339%	295,009

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: BTBD7
Protein: p.Ala983Pro
Coding: c.2947G>C
MANE Select: NM_001002860
dbSNP: rs147201730
Type: single nucleotide variant
Location: chr14:93242725 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 61.50
Residue 983: the 'disordered' region

Full BTBD7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BTBD7 p.Ala110Thr Uncertain significance ★ ⚠ same type
BTBD7 p.Ala158Thr Uncertain significance ★ ⚠ same type
BTBD7 p.Ala359Ser Uncertain significance ★ ⚠ same type
BTBD7 p.Ala3Val Uncertain significance ★ ⚠ same type
BTBD7 p.Ala491Asp Uncertain significance ★ ⚠ same type
BTBD7 p.Ala567Ser Uncertain significance ★ ⚠ same type
BTBD7 p.Ala567Val Uncertain significance ★ ⚠ same type
BTBD7 p.Ala675Ser 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/btbd7-p-ala983pro (accessed [today's date]).

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