Is BLTP2 p.Arg1648Gln (c.4943G>A) pathogenic?

BLTP2 p.Arg1648Gln (c.4943G>A) is classified Uncertain significance in BLTP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). AlphaMissense: likely benign (0.0642); Very rare (popmax 0.00446%, eas).

How common is BLTP2 p.Arg1648Gln (c.4943G>A) in the general population?

BLTP2 p.Arg1648Gln (c.4943G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about BLTP2 p.Arg1648Gln (c.4943G>A)?

AlphaMissense predicts likely benign (score 0.0642) — an in-silico prediction, not a clinical call.

BLTP2 p.Arg1648Gln

c.4943G>A · rs143431869 · VCV3134311

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0642 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0642	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -5.66	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 9,298 bp · p 1.1e-21 · regional, not allelic
Overall
CADD	22.0	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 0.00446% East Asian · 2/44,888 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000718%

Overall 0.0013% 21/1,614,004 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,444
Remaining individualsnot grpmax-eligible	0.0016%	62,506
European (non-Finnish)	0.00144%	69,406
African / African-American	0.00133%	75,030

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: BLTP2
Protein: p.Arg1648Gln
Coding: c.4943G>A
MANE Select: NM_014680
dbSNP: rs143431869
Type: single nucleotide variant
Location: chr17:28623776 (GRCh38)
Structure: AlphaFold pLDDT 71.37

Full BLTP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BLTP2 p.Arg1648Gly Uncertain significance ★ ⚠ same residue
BLTP2 p.Ala1395Ser Uncertain significance ★ ⚠ same type
BLTP2 p.Ala1564Thr Uncertain significance ★ ⚠ same type
BLTP2 p.Ala1826Thr Uncertain significance ★ ⚠ same type
BLTP2 p.Ala248Thr Uncertain significance ★ ⚠ same type
BLTP2 p.Ala324Thr Uncertain significance ★ ⚠ same type
BLTP2 p.Ala393Thr Uncertain significance ★ ⚠ same type
BLTP2 p.Ala539Thr 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/bltp2-p-arg1648gln (accessed [today's date]).

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