Is BLTP1 p.Ile667Val (c.1999A>G) pathogenic?

BLTP1 p.Ile667Val (c.1999A>G) is classified Uncertain significance in BLTP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-08). AlphaMissense: likely benign (0.067); Ultra-rare (popmax 0.0284%, amr).

How common is BLTP1 p.Ile667Val (c.1999A>G) in the general population?

BLTP1 p.Ile667Val (c.1999A>G) is ultra-rare (popmax 0.0284%, amr) (gnomAD).

What do computational predictors say about BLTP1 p.Ile667Val (c.1999A>G)?

AlphaMissense predicts likely benign (score 0.067) — an in-silico prediction, not a clinical call.

BLTP1 p.Ile667Val

c.1999A>G · rs760842276 · VCV3134179

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.067 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0284%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.067	likely benign
REVEL	0.027	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 5.4	GERP 1.4, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 45 kb · p 1e-08 · regional, not allelic
Overall
CADD	18.32	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0284% Admixed American · 17/59,958 alleles

Filtering AF 0.018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.00533% 86/1,613,472 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0284%	3,527
East Asian	0.0201%	4,979
Remaining individualsnot grpmax-eligible	0.0128%	7,805
South Asian	0.00439%	22,769
African / African-American	0.00401%	24,962
European (non-Finnish)	0.00373%	26,812
Finnishnot grpmax-eligible	0.00156%	64,006

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.Ile667Val
Coding: c.1999A>G
MANE Select: NM_001384125
dbSNP: rs760842276
Type: single nucleotide variant
Location: chr4:122209885 (GRCh38)
Residue 667: 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.Ile667Leu 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-ile667val (accessed [today's date]).

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