Is BTBD1 p.Arg79Ser (c.235C>A) pathogenic?

BTBD1 p.Arg79Ser (c.235C>A) is classified Uncertain significance in BTBD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-24). AlphaMissense: likely benign (0.1661); Very rare (popmax 8.72e-05%, nfe).

How common is BTBD1 p.Arg79Ser (c.235C>A) in the general population?

BTBD1 p.Arg79Ser (c.235C>A) is very rare (popmax 8.72e-05%, nfe) (gnomAD).

What do computational predictors say about BTBD1 p.Arg79Ser (c.235C>A)?

AlphaMissense predicts likely benign (score 0.1661) — an in-silico prediction, not a clinical call.

BTBD1 p.Arg79Ser

c.235C>A · VCV3261979

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1661 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.72e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1661	likely benign
REVEL	0.24	benign-leaning
SaProt	LLR -5.89	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 11	GERP 0.61, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 326 bp · p 0.48 · regional, not allelic
Overall
CADD	20.8	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 8.72e-05% European (non-Finnish) · 1/1,146,218 alleles

Overall 7.23e-05% 1/1,382,702 alleles · very rare

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: BTBD1
Protein: p.Arg79Ser
Coding: c.235C>A
MANE Select: NM_025238
Type: single nucleotide variant
Location: chr15:83066917 (GRCh38)
Gene constraint: LOEUF 1.105 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.99
Residue 79: the btb domain; a modified residue (omega-n-methylarginine)

Full BTBD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BTBD1 p.Ala162Gly Uncertain significance ★ ⚠ same type
BTBD1 p.Ala162Val Uncertain significance ★ ⚠ same type
BTBD1 p.Ala16Gly Uncertain significance ★ ⚠ same type
BTBD1 p.Ala23Pro Uncertain significance ★ ⚠ same type
BTBD1 p.Ala82Val Uncertain significance ★ ⚠ same type
BTBD1 p.Ala84Val Uncertain significance ★ ⚠ same type
BTBD1 p.Ala8Thr Uncertain significance ★ ⚠ same type
BTBD1 p.Arg236Gln 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/btbd1-p-arg79ser (accessed [today's date]).

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