Is BLTP2 p.Ile1775Val (c.5323A>G) pathogenic?

BLTP2 p.Ile1775Val (c.5323A>G) is classified Uncertain significance in BLTP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-16). AlphaMissense: likely benign (0.1552); Ultra-rare (popmax 0.0801%, sas).

How common is BLTP2 p.Ile1775Val (c.5323A>G) in the general population?

BLTP2 p.Ile1775Val (c.5323A>G) is ultra-rare (popmax 0.0801%, sas) (gnomAD).

What do computational predictors say about BLTP2 p.Ile1775Val (c.5323A>G)?

AlphaMissense predicts likely benign (score 0.1552) — an in-silico prediction, not a clinical call.

BLTP2 p.Ile1775Val

c.5323A>G · VCV3991801

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1552 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0801%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1552	likely benign
REVEL	0.286	benign-leaning
SaProt	LLR -4.68	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 7.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 9,298 bp · p 1.1e-21 · regional, not allelic
Overall
CADD	22.8	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 0.0801% South Asian · 73/91,088 alleles

Filtering AF 0.0654% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0599%

Overall 0.00564% 91/1,614,096 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0801%	1,248
Admixed American	0.00833%	12,000
East Asian	0.00223%	44,900
European (non-Finnish)	0.00102%	98,337

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.Ile1775Val
Coding: c.5323A>G
MANE Select: NM_014680
Type: single nucleotide variant
Location: chr17:28620550 (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.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
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-ile1775val (accessed [today's date]).

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