Is BLTP2 p.Lys577Glu (c.1729A>G) pathogenic?

BLTP2 p.Lys577Glu (c.1729A>G) is classified Uncertain significance in BLTP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-06). AlphaMissense: likely pathogenic (0.6245); Very rare (popmax 0.00203%, nfe).

How common is BLTP2 p.Lys577Glu (c.1729A>G) in the general population?

BLTP2 p.Lys577Glu (c.1729A>G) is very rare (popmax 0.00203%, nfe) (gnomAD).

What do computational predictors say about BLTP2 p.Lys577Glu (c.1729A>G)?

AlphaMissense predicts likely pathogenic (score 0.6245) — an in-silico prediction, not a clinical call.

BLTP2 p.Lys577Glu

c.1729A>G · rs2508690446 · VCV3134272

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6245 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00203%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6245	likely pathogenic
REVEL	0.09	moderately benign-leaning
SaProt	LLR -9.80	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.48 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 10 kb · p 0.6 · regional, not allelic
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00203% European (non-Finnish) · 24/1,180,024 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00149% 24/1,614,168 alleles · very rare exomes 24/1,461,858 · genomes 0/152,310 · joint denominator

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.Lys577Glu
Coding: c.1729A>G
MANE Select: NM_014680
dbSNP: rs2508690446
Type: single nucleotide variant
Location: chr17:28637878 (GRCh38)
Structure: AlphaFold pLDDT 71.37

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

Similar variants

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
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-lys577glu (accessed [today's date]).

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