Is BLTP1 p.Pro904= (c.2712T>A) pathogenic?

BLTP1 p.Pro904= (c.2712T>A) is classified Benign in BLTP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-26). Common (popmax 47.1%, sas) — too common for a highly-penetrant pathogenic allele; Associated with Alkuraya-Kucinskas syndrome.

What condition is associated with BLTP1 p.Pro904= (c.2712T>A)?

BLTP1 p.Pro904= (c.2712T>A) is associated with Alkuraya-Kucinskas syndrome (ClinVar).

BLTP1 p.Pro904=

Q: How common is BLTP1 p.Pro904= (c.2712T>A) in the general population?

BLTP1 p.Pro904= (c.2712T>A) is common (popmax 47.1%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.2712T>A · rs7658836 · VCV1271909

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 47.1%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

Alkuraya-Kucinskas syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.266	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.14	GERP -1.4, phastCons 0.35
Overall
CADD	8.594	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 47.1% South Asian · 42,889/91,066 alleles

Filtering AF 46.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 46.6%

Overall 30.2% 486,966/1,613,808 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	47.1%	2
Middle Eastern	45.3%	2
Ashkenazi Jewishnot grpmax-eligible	41.5%	2
East Asian	35.9%	3
Amishnot grpmax-eligible	34.5%	3
Remaining individualsnot grpmax-eligible	32.4%	3
Admixed American	30%	3
Finnishnot grpmax-eligible	29.8%	3
European (non-Finnish)	29.6%	3
African / African-American	8.13%	12

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: BLTP1
Protein: p.Pro904=
Coding: c.2712T>A
MANE Select: NM_001384125
dbSNP: rs7658836
Type: single nucleotide variant
Location: chr4:122224596 (GRCh38)
Residue 904: 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.Pro904Leu Uncertain significance ★ ⚠ same residue
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

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-pro904 (accessed [today's date]).

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