Is BLTP1 p.Pro192Arg (c.575C>G) pathogenic?

BLTP1 p.Pro192Arg (c.575C>G) is classified Conflicting classifications of pathogenicity in BLTP1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2020-10-19). AlphaMissense: likely benign (0.1822); Rare (popmax 0.36%, eas); Associated with Alkuraya-Kucinskas syndrome.

What condition is associated with BLTP1 p.Pro192Arg (c.575C>G)?

BLTP1 p.Pro192Arg (c.575C>G) is associated with Alkuraya-Kucinskas syndrome (ClinVar).

How common is BLTP1 p.Pro192Arg (c.575C>G) in the general population?

BLTP1 p.Pro192Arg (c.575C>G) is rare (popmax 0.36%, eas) (gnomAD).

What do computational predictors say about BLTP1 p.Pro192Arg (c.575C>G)?

AlphaMissense predicts likely benign (score 0.1822) — an in-silico prediction, not a clinical call.

BLTP1 p.Pro192Arg

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.575C>G · rs188182890 · VCV809676

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1822 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.36%, eas)

Conditions

Alkuraya-Kucinskas syndrome

Computational evidence

Protein change
AlphaMissense	0.1822	likely benign
REVEL	0.604	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 17 kb · p 0.0013 · regional, not allelic
Overall
CADD	22.3	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

Grpmax group 0.36% East Asian · 161/44,714 alleles

Filtering AF 0.315% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.297%

Overall 0.0176% 283/1,611,974 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.36%	278
Remaining individualsnot grpmax-eligible	0.0977%	1,023
South Asian	0.0341%	2,931
African / African-American	0.032%	3,123
Admixed American	0.00334%	29,966
European (non-Finnish)	0.000339%	294,652

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.Pro192Arg
Coding: c.575C>G
MANE Select: NM_001384125
dbSNP: rs188182890
Type: single nucleotide variant
Location: chr4:122187460 (GRCh38)

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-pro192arg (accessed [today's date]).

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