Is BLTP1 p.Ile4496Val (c.13486A>G) pathogenic?

BLTP1 p.Ile4496Val (c.13486A>G) is classified Uncertain significance in BLTP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-19). AlphaMissense: likely benign (0.0705); Ultra-rare (popmax 0.0112%, eas).

How common is BLTP1 p.Ile4496Val (c.13486A>G) in the general population?

BLTP1 p.Ile4496Val (c.13486A>G) is ultra-rare (popmax 0.0112%, eas) (gnomAD).

What do computational predictors say about BLTP1 p.Ile4496Val (c.13486A>G)?

AlphaMissense predicts likely benign (score 0.0705) — an in-silico prediction, not a clinical call.

BLTP1 p.Ile4496Val

c.13486A>G · rs781305534 · VCV3134164

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0705 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, eas)

Computational evidence

Protein change
AlphaMissense	0.0705	likely benign
REVEL	0.543	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 4, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 1,297 bp · p 6.3e-11 · regional, not allelic
Overall
CADD	20.6	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 I4408V vs ClinVar I4496V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0112% East Asian · 5/44,816 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00112% 18/1,612,494 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0112%	8,963
Admixed American	0.00668%	14,966
Remaining individualsnot grpmax-eligible	0.0016%	62,422
European (non-Finnish)	0.000678%	147,395

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.Ile4496Val
Coding: c.13486A>G
MANE Select: NM_001384125
dbSNP: rs781305534
Type: single nucleotide variant
Location: chr4:122348659 (GRCh38)
Residue 4496: 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.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
BLTP1 p.Arg3665Gln 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-ile4496val (accessed [today's date]).

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