Is BLTP2 p.Arg1230Trp (c.3688C>T) pathogenic?

BLTP2 p.Arg1230Trp (c.3688C>T) is classified Uncertain significance in BLTP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-11). AlphaMissense: likely benign (0.1869); Very rare (popmax 0.00539%, afr).

How common is BLTP2 p.Arg1230Trp (c.3688C>T) in the general population?

BLTP2 p.Arg1230Trp (c.3688C>T) is very rare (popmax 0.00539%, afr) (gnomAD).

What do computational predictors say about BLTP2 p.Arg1230Trp (c.3688C>T)?

AlphaMissense predicts likely benign (score 0.1869) — an in-silico prediction, not a clinical call.

BLTP2 p.Arg1230Trp

c.3688C>T · rs759113307 · VCV3134303

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1869 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00539%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1869	likely benign
REVEL	0.101	moderately benign-leaning
SaProt	LLR -4.31	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 4.7	GERP -1.2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 8,974 bp · p 0.0049 · regional, not allelic
Overall
CADD	24.4	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 0.00539% African / African-American · 4/74,220 alleles

Filtering AF 0.00176% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00105%

Overall 0.00126% 20/1,591,494 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00539%	18,555
Ashkenazi Jewishnot grpmax-eligible	0.00359%	27,866
Remaining individualsnot grpmax-eligible	0.00326%	30,716
European (non-Finnish)	0.00111%	89,932

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.Arg1230Trp
Coding: c.3688C>T
MANE Select: NM_014680
dbSNP: rs759113307
Type: single nucleotide variant
Location: chr17:28633059 (GRCh38)
Structure: AlphaFold pLDDT 71.37

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

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BLTP2 p.Ala248Thr Uncertain significance ★ ⚠ same type
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BLTP2 p.Ala393Thr Uncertain significance ★ ⚠ same type
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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-arg1230trp (accessed [today's date]).

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