Is BTBD7 p.Pro813Ser (c.2437C>T) pathogenic?

BTBD7 p.Pro813Ser (c.2437C>T) is classified Uncertain significance in BTBD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely benign (0.0684); Rare (popmax 0.215%, mid).

How common is BTBD7 p.Pro813Ser (c.2437C>T) in the general population?

BTBD7 p.Pro813Ser (c.2437C>T) is rare (popmax 0.215%, mid) (gnomAD).

What do computational predictors say about BTBD7 p.Pro813Ser (c.2437C>T)?

AlphaMissense predicts likely benign (score 0.0684) — an in-silico prediction, not a clinical call.

BTBD7 p.Pro813Ser

c.2437C>T · rs143877217 · VCV3135445

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0684 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.215%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0684	likely benign
REVEL	0.169	moderately benign-leaning
SaProt	LLR -6.65	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 5.1	GERP 0.92, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 4,007 bp · p 0.18 · regional, not allelic
Overall
CADD	18.24	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 0.215% Middle Eastern · 13/6,060 alleles

Filtering AF 0.127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.101%

Overall 0.0271% 438/1,614,162 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.215%	466
Admixed American	0.108%	923
Remaining individualsnot grpmax-eligible	0.064%	1,563
Ashkenazi Jewishnot grpmax-eligible	0.0405%	2,467
European (non-Finnish)	0.0251%	3,987
African / African-American	0.008%	12,505
South Asian	0.00549%	18,216
East Asian	0.00223%	44,880

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.Pro813Ser
Coding: c.2437C>T
MANE Select: NM_001002860
dbSNP: rs143877217
Type: single nucleotide variant
Location: chr14:93245971 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 61.50

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-pro813ser (accessed [today's date]).

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