Is KBTBD13 p.Pro433= (c.1299C>T) pathogenic?

KBTBD13 p.Pro433= (c.1299C>T) is classified Likely benign in KBTBD13 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-05). Very rare (popmax 0.000172%, nfe); Associated with nemaline myopathy 6.

What condition is associated with KBTBD13 p.Pro433= (c.1299C>T)?

KBTBD13 p.Pro433= (c.1299C>T) is associated with nemaline myopathy 6 (ClinVar).

How common is KBTBD13 p.Pro433= (c.1299C>T) in the general population?

KBTBD13 p.Pro433= (c.1299C>T) is very rare (popmax 0.000172%, nfe) (gnomAD).

How is Childhood-onset nemaline myopathy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

KBTBD13 p.Pro433=

c.1299C>T · rs752673644 · VCV2185367

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000172%, nfe)

Conditions

nemaline myopathy 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -20	GERP -3.3
Overall
CADD	0.091	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000172% European (non-Finnish) · 2/1,164,316 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000127% 2/1,570,594 alleles · very rare exomes 2/1,418,212 · genomes 0/152,382 · 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: KBTBD13
Protein: p.Pro433=
Coding: c.1299C>T
MANE Select: NM_001101362
dbSNP: rs752673644
Type: single nucleotide variant
Location: chr15:65078114 (GRCh38)
Gene constraint: LOEUF 1.961 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.56

Full KBTBD13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

nemaline myopathy 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Childhood-onset nemaline myopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

KBTBD13 p.Pro433Ser Uncertain significance ★★ ⚠ same residue
KBTBD13 p.Lys390Asn Likely pathogenic ★★ ⚠ same condition
KBTBD13 p.Ala112Glu Uncertain significance ★★ same condition
KBTBD13 p.Ala192Glu Uncertain significance ★★ ⚠ same condition
KBTBD13 p.Ala262Thr Uncertain significance ★★ ⚠ same condition
KBTBD13 p.Ala301Ser Uncertain significance ★★ ⚠ same condition
KBTBD13 p.Ala324Thr Uncertain significance ★★ ⚠ same condition
KBTBD13 p.Ala396Val Uncertain significance ★★ ⚠ same condition

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/kbtbd13-p-pro433 (accessed [today's date]).

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