Is BLTP1 p.Arg1791Lys (c.5372G>A) pathogenic?

BLTP1 p.Arg1791Lys (c.5372G>A) is classified Uncertain significance in BLTP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-07-08). AlphaMissense: likely benign (0.0766); Rare (popmax 0.172%, eas).

How common is BLTP1 p.Arg1791Lys (c.5372G>A) in the general population?

BLTP1 p.Arg1791Lys (c.5372G>A) is rare (popmax 0.172%, eas) (gnomAD).

What do computational predictors say about BLTP1 p.Arg1791Lys (c.5372G>A)?

AlphaMissense predicts likely benign (score 0.0766) — an in-silico prediction, not a clinical call.

BLTP1 p.Arg1791Lys

c.5372G>A · rs200778020 · VCV1205997

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0766 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.172%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0766	likely benign
REVEL	0.237	benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	Δ0.27	donor loss at this position · masked 0 · deltas
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 9,909 bp · p 0.01 · regional, not allelic
Overall
CADD	19.39	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 0.172% East Asian · 77/44,840 alleles

Filtering AF 0.141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.129%

Overall 0.0144% 233/1,613,338 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.172%	582
Finnishnot grpmax-eligible	0.0969%	1,032
Remaining individualsnot grpmax-eligible	0.0176%	5,680
Middle Eastern	0.0165%	6,060
South Asian	0.0143%	7,004
European (non-Finnish)	0.00577%	17,345
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,590

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.Arg1791Lys
Coding: c.5372G>A
MANE Select: NM_001384125
dbSNP: rs200778020
Type: single nucleotide variant
Location: chr4:122247217 (GRCh38)
Residue 1791: 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.Arg2095His Uncertain significance ★★ same type
BLTP1 p.Arg2279Cys Uncertain significance ★★ same type
BLTP1 p.Arg3665Gln Uncertain significance ★★ ⚠ same type
BLTP1 p.Arg3884Trp 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-arg1791lys (accessed [today's date]).

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