Is BLTP1 p.Arg4347Cys (c.13039C>T) pathogenic?

BLTP1 p.Arg4347Cys (c.13039C>T) is classified Uncertain significance in BLTP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-11). AlphaMissense: likely pathogenic (0.9992); Very rare (popmax 0.0022%, sas).

How common is BLTP1 p.Arg4347Cys (c.13039C>T) in the general population?

BLTP1 p.Arg4347Cys (c.13039C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about BLTP1 p.Arg4347Cys (c.13039C>T)?

AlphaMissense predicts likely pathogenic (score 0.9992) — an in-silico prediction, not a clinical call.

BLTP1 p.Arg4347Cys

c.13039C>T · VCV3261112

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9992 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Computational evidence

Protein change
AlphaMissense	0.9992	likely pathogenic · top 1% in BLTP1
REVEL	0.477	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 4.2, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 4,095 bp · p 3.3e-07 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R4259C vs ClinVar R4347C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,014 alleles

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

Overall 0.000342% 5/1,460,978 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,507
European (non-Finnish)	0.000254%	393,122

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.Arg4347Cys
Coding: c.13039C>T
MANE Select: NM_001384125
Type: single nucleotide variant
Location: chr4:122346664 (GRCh38)
Residue 4347: the 'disordered' region; a UniProt-annotated variant site (in alkkucs)

Full BLTP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BLTP1 p.Arg4347His Uncertain significance ★ same residue
BLTP1 p.Arg968Cys Likely pathogenic ★★ ⚠ same type
BLTP1 c.1498+4A>G Uncertain significance ★★ same type
BLTP1 p.Ala2332Thr Uncertain significance ★★ ⚠ same type
BLTP1 p.Arg1317His Uncertain significance ★★ same type
BLTP1 p.Arg1791Lys Uncertain significance ★★ ⚠ same type
BLTP1 p.Arg2095His Uncertain significance ★★ same type
BLTP1 p.Arg2279Cys Uncertain significance ★★ same type

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-arg4347cys (accessed [today's date]).

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