Is BLTP1 p.Arg1958Gln (c.5873G>A) pathogenic?

BLTP1 p.Arg1958Gln (c.5873G>A) is classified Likely benign in BLTP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-05). AlphaMissense: likely benign (0.0667); Very rare (popmax 0.0022%, sas); Associated with Alkuraya-Kucinskas syndrome.

What condition is associated with BLTP1 p.Arg1958Gln (c.5873G>A)?

BLTP1 p.Arg1958Gln (c.5873G>A) is associated with Alkuraya-Kucinskas syndrome (ClinVar).

How common is BLTP1 p.Arg1958Gln (c.5873G>A) in the general population?

BLTP1 p.Arg1958Gln (c.5873G>A) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about BLTP1 p.Arg1958Gln (c.5873G>A)?

AlphaMissense predicts likely benign (score 0.0667) — an in-silico prediction, not a clinical call.

BLTP1 p.Arg1958Gln

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.5873G>A · VCV4814172

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0667 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Alkuraya-Kucinskas syndrome

Computational evidence

Protein change
AlphaMissense	0.0667	likely benign
REVEL	0.066	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 21 kb · p 3.1e-07 · regional, not allelic
Overall
CADD	22.5	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 0.0022% South Asian · 2/91,064 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000616% 9/1,461,496 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00469%	21,331
South Asiangrpmax	0.0022%	45,532
African / African-American	0.00133%	74,974
European (non-Finnish)	0.000254%	393,224

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg1958Gln
Coding: c.5873G>A
MANE Select: NM_001384125
Type: single nucleotide variant
Location: chr4:122250524 (GRCh38)
Residue 1958: the 'disordered' region; a UniProt-annotated variant site (in alkkucs); a UniProt-annotated variant site (in alkkucs; uncertain significance)

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-arg1958gln (accessed [today's date]).

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