Is BLTP1 p.Cys1502Ser (c.4504T>A) pathogenic?

BLTP1 p.Cys1502Ser (c.4504T>A) is classified Uncertain significance in BLTP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-15). AlphaMissense: ambiguous (0.3783); Absent from gnomAD v4.1; Associated with Alkuraya-Kucinskas syndrome.

What condition is associated with BLTP1 p.Cys1502Ser (c.4504T>A)?

BLTP1 p.Cys1502Ser (c.4504T>A) is associated with Alkuraya-Kucinskas syndrome (ClinVar).

How common is BLTP1 p.Cys1502Ser (c.4504T>A) in the general population?

BLTP1 p.Cys1502Ser (c.4504T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BLTP1 p.Cys1502Ser (c.4504T>A)?

AlphaMissense predicts ambiguous (score 0.3783) — an in-silico prediction, not a clinical call.

BLTP1 p.Cys1502Ser

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.4504T>A · VCV3376185

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3783 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Alkuraya-Kucinskas syndrome

Computational evidence

Protein change
AlphaMissense	0.3783	ambiguous
REVEL	0.25	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 9,909 bp · p 0.01 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BLTP1
Protein: p.Cys1502Ser
Coding: c.4504T>A
MANE Select: NM_001384125
Type: single nucleotide variant
Location: chr4:122240186 (GRCh38)
Residue 1502: 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.Arg968Cys Likely pathogenic ★★ ⚠ same condition
BLTP1 p.Arg3665Gln Uncertain significance ★★ ⚠ same condition
BLTP1 p.Arg3884Trp Uncertain significance ★★ same condition
BLTP1 p.Arg50Trp Uncertain significance ★★ same condition
BLTP1 p.Asp3074Glu Uncertain significance ★★ ⚠ same condition
BLTP1 p.Asp998Tyr Uncertain significance ★★ ⚠ same condition
BLTP1 p.Gln1511His Uncertain significance ★★ ⚠ same condition
BLTP1 p.Gly1016Ser 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-cys1502ser (accessed [today's date]).

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