Is BLTP2 p.Ser2199Leu (c.6596C>T) pathogenic?

BLTP2 p.Ser2199Leu (c.6596C>T) is classified Uncertain significance in BLTP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-21). AlphaMissense: likely benign (0.0749); Very rare (popmax 0.00659%, sas).

How common is BLTP2 p.Ser2199Leu (c.6596C>T) in the general population?

BLTP2 p.Ser2199Leu (c.6596C>T) is very rare (popmax 0.00659%, sas) (gnomAD).

What do computational predictors say about BLTP2 p.Ser2199Leu (c.6596C>T)?

AlphaMissense predicts likely benign (score 0.0749) — an in-silico prediction, not a clinical call.

BLTP2 p.Ser2199Leu

c.6596C>T · VCV3824572

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0749 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0749	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -6.05	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 8.6	GERP 0.77, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 9,298 bp · p 1.1e-21 · regional, not allelic
Overall
CADD	22.4	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 0.00659% South Asian · 6/91,080 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.00105% 17/1,613,968 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,180
Remaining individualsnot grpmax-eligible	0.0032%	31,242
European (non-Finnish)	0.000763%	131,111

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.Ser2199Leu
Coding: c.6596C>T
MANE Select: NM_014680
Type: single nucleotide variant
Location: chr17:28615176 (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-ser2199leu (accessed [today's date]).

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