Is BLTP1 p.Arg4285Gln (c.12854G>A) pathogenic?

BLTP1 p.Arg4285Gln (c.12854G>A) is classified Uncertain significance in BLTP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-16). AlphaMissense: likely pathogenic (0.9352); Very rare (popmax 0.0022%, sas).

How common is BLTP1 p.Arg4285Gln (c.12854G>A) in the general population?

BLTP1 p.Arg4285Gln (c.12854G>A) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about BLTP1 p.Arg4285Gln (c.12854G>A)?

AlphaMissense predicts likely pathogenic (score 0.9352) — an in-silico prediction, not a clinical call.

BLTP1 p.Arg4285Gln

c.12854G>A · VCV3824533

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9352 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Computational evidence

Protein change
AlphaMissense	0.9352	likely pathogenic
REVEL	0.358	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.29	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 12	GERP 4.3, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 4,095 bp · p 3.3e-07 · regional, not allelic
Overall
CADD	25.1	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 R4197Q vs ClinVar R4285Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,070 alleles

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

Overall 0.00041% 6/1,461,652 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,535
Admixed American	0.00167%	59,972
Remaining individualsnot grpmax-eligible	0.0016%	62,494
European (non-Finnish)	0.00017%	589,929

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.Arg4285Gln
Coding: c.12854G>A
MANE Select: NM_001384125
Type: single nucleotide variant
Location: chr4:122344418 (GRCh38)
Residue 4285: 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.Arg4285Ter Likely pathogenic ★ 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-arg4285gln (accessed [today's date]).

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