Is BLTP2 p.Ile1838Val (c.5512A>G) pathogenic?

BLTP2 p.Ile1838Val (c.5512A>G) is classified Uncertain significance in BLTP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-18). AlphaMissense: likely benign (0.0635); Very rare (popmax 0.00441%, nfe).

How common is BLTP2 p.Ile1838Val (c.5512A>G) in the general population?

BLTP2 p.Ile1838Val (c.5512A>G) is very rare (popmax 0.00441%, nfe) (gnomAD).

What do computational predictors say about BLTP2 p.Ile1838Val (c.5512A>G)?

AlphaMissense predicts likely benign (score 0.0635) — an in-silico prediction, not a clinical call.

BLTP2 p.Ile1838Val

c.5512A>G · VCV4646096

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0635 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00441%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0635	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -5.01	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.23	donor loss, 8 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -0.021	GERP -2.7, phastCons 0.51
Regional constraint	o/e 0.67	unconstrained · MANE · 9,298 bp · p 1.1e-21 · regional, not allelic
Overall
CADD	10.98	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 0.00441% European (non-Finnish) · 52/1,180,048 alleles

Filtering AF 0.00342% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0031%

Overall 0.00335% 54/1,613,874 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00441%	22,693
Remaining individualsnot grpmax-eligible	0.0016%	62,484
African / African-American	0.00133%	74,944

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.Ile1838Val
Coding: c.5512A>G
MANE Select: NM_014680
Type: single nucleotide variant
Location: chr17:28619868 (GRCh38)
Structure: AlphaFold pLDDT 71.37

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

Similar variants

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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
BLTP2 p.Ala694Gly 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-ile1838val (accessed [today's date]).

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