Is BLTP1 p.Arg1430Ter (c.4287dup) pathogenic?

BLTP1 p.Arg1430Ter (c.4287dup) is classified Pathogenic in BLTP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-24). Absent from gnomAD; Associated with Alkuraya-Kucinskas syndrome.

What condition is associated with BLTP1 p.Arg1430Ter (c.4287dup)?

BLTP1 p.Arg1430Ter (c.4287dup) is associated with Alkuraya-Kucinskas syndrome (ClinVar).

How common is BLTP1 p.Arg1430Ter (c.4287dup) in the general population?

BLTP1 p.Arg1430Ter (c.4287dup) is absent from gnomAD (gnomAD).

BLTP1 p.Arg1430Ter

Q: How is KIAA1109-related early lethal congenital brain malformations-arthrogryposis syndrome inherited?

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

c.4287dup · rs2148690880 · VCV1323144

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Alkuraya-Kucinskas syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 29 of 88
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.8	GERP 2.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BLTP1
Protein: p.Arg1430Ter
Coding: c.4287dup
MANE Select: NM_001384125
dbSNP: rs2148690880
Type: Duplication
Location: chr4:122239968 (GRCh38)
Residue 1430: a UniProt-annotated variant site (in alkkucs)

Full BLTP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Alkuraya-Kucinskas syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For KIAA1109-related early lethal congenital brain malformations-arthrogryposis syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal

Similar variants

BLTP1 p.Asn3735fs Likely pathogenic ★ same condition
BLTP1 p.Val3124_Ile3125insTer Pathogenic ★ same condition
BLTP1 c.2209_2247+201dup Uncertain significance ★ same condition
BLTP1 c.5184+28dup Uncertain significance ★ same condition
BLTP1 c.901+49_901+53dup Uncertain significance ★ same condition
BLTP1 p.Arg968Cys Likely pathogenic ★★ ⚠ same condition
BLTP1 p.Arg3665Gln Uncertain significance ★★ ⚠ same condition
BLTP1 p.Arg3884Trp 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/bltp1-p-arg1430ter (accessed [today's date]).

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