Is BLTP1 p.Arg968Cys (c.2902C>T) pathogenic?

BLTP1 p.Arg968Cys (c.2902C>T) is classified Likely pathogenic in BLTP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-01-09). AlphaMissense: likely benign (0.144); Very rare (popmax 0.00017%, nfe); Associated with KIAA1109-related disorders.

What condition is associated with BLTP1 p.Arg968Cys (c.2902C>T)?

BLTP1 p.Arg968Cys (c.2902C>T) is associated with KIAA1109-related disorders, Alkuraya-Kucinskas syndrome (ClinVar).

How common is BLTP1 p.Arg968Cys (c.2902C>T) in the general population?

BLTP1 p.Arg968Cys (c.2902C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about BLTP1 p.Arg968Cys (c.2902C>T)?

AlphaMissense predicts likely benign (score 0.144) — an in-silico prediction, not a clinical call.

BLTP1 p.Arg968Cys

c.2902C>T · rs1051597475 · VCV487550

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.144 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

KIAA1109-related disorders

Computational evidence

Protein change
AlphaMissense	0.144	likely benign ⚠ discordant with ClinVar
REVEL	0.312	indeterminate
Splicing
SpliceAI	Δ0.52	donor loss · deltas
Pangolin	Δ0.55	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 45 kb · p 1e-08 · regional, not allelic
Overall
CADD	26.9	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 0.00017% European (non-Finnish) · 2/1,178,652 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,456,852 alleles · very rare

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.Arg968Cys
Coding: c.2902C>T
MANE Select: NM_001384125
dbSNP: rs1051597475
Type: single nucleotide variant
Location: chr4:122226815 (GRCh38)
Residue 968: 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

KIAA1109-related disorders

Also linked: Alkuraya-Kucinskas syndrome

Similar variants

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
BLTP1 p.His3063Arg 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-arg968cys (accessed [today's date]).

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