Is BTBD17 p.Pro345= (c.1035G>A) pathogenic?

BTBD17 p.Pro345= (c.1035G>A) is classified Likely benign in BTBD17 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-01). Ultra-rare (popmax 0.0143%, afr).

How common is BTBD17 p.Pro345= (c.1035G>A) in the general population?

BTBD17 p.Pro345= (c.1035G>A) is ultra-rare (popmax 0.0143%, afr) (gnomAD).

BTBD17 p.Pro345=

c.1035G>A · rs775686353 · VCV2648212

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0143%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.2	GERP -2.8
Overall
CADD	3.721	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0143% African / African-American · 10/69,778 alleles

Filtering AF 0.00772% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00586%

Overall 0.000652% 10/1,532,794 alleles · ultra-rare exomes 5/1,380,720 · genomes 5/152,074 · joint denominator

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: BTBD17
Protein: p.Pro345=
Coding: c.1035G>A
MANE Select: NM_001080466
dbSNP: rs775686353
Type: single nucleotide variant
Location: chr17:74357059 (GRCh38)
Gene constraint: LOEUF 1.489 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.20

Full BTBD17 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BTBD17 p.Ala113Thr Uncertain significance ★ ⚠ same type
BTBD17 p.Ala160Val Uncertain significance ★ ⚠ same type
BTBD17 p.Ala248Thr Uncertain significance ★ ⚠ same type
BTBD17 p.Ala254Val Uncertain significance ★ ⚠ same type
BTBD17 p.Ala301Val Uncertain significance ★ ⚠ same type
BTBD17 p.Ala310Thr Uncertain significance ★ ⚠ same type
BTBD17 p.Ala350Glu Uncertain significance ★ ⚠ same type
BTBD17 p.Ala350Ser 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/btbd17-p-pro345 (accessed [today's date]).

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