Is BLTP1 p.Val4093Leu (c.12277G>C) pathogenic?

BLTP1 p.Val4093Leu (c.12277G>C) is classified Conflicting classifications of pathogenicity in BLTP1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-01-01). AlphaMissense: likely benign (0.0969); Rare (popmax 0.541%, afr).

How common is BLTP1 p.Val4093Leu (c.12277G>C) in the general population?

BLTP1 p.Val4093Leu (c.12277G>C) is rare (popmax 0.541%, afr) (gnomAD).

What do computational predictors say about BLTP1 p.Val4093Leu (c.12277G>C)?

AlphaMissense predicts likely benign (score 0.0969) — an in-silico prediction, not a clinical call.

BLTP1 p.Val4093Leu

c.12277G>C · rs200028937 · VCV2563958

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0969 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.541%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0969	likely benign
REVEL	0.046	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 1.2	GERP -3, phastCons 0.72
Regional constraint	o/e 0.74	unconstrained · MANE · 695 bp · p 0.031 · regional, not allelic
Overall
CADD	12.94	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 V4005L vs ClinVar V4093L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.541% African / African-American · 399/73,740 alleles

Filtering AF 0.497% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.48%

Overall 0.027% 431/1,594,582 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.541%	185
Remaining individualsnot grpmax-eligible	0.0291%	3,432
Admixed American	0.0182%	5,483
Middle Eastern	0.0167%	5,992
European (non-Finnish)	0.000256%	391,137

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.Val4093Leu
Coding: c.12277G>C
MANE Select: NM_001384125
dbSNP: rs200028937
Type: single nucleotide variant
Location: chr4:122336883 (GRCh38)
Residue 4093: 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.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-val4093leu (accessed [today's date]).

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