Is BLTP2 p.Phe1091Leu (c.3271T>C) pathogenic?

BLTP2 p.Phe1091Leu (c.3271T>C) is classified Uncertain significance in BLTP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-13). AlphaMissense: ambiguous (0.4174); Ultra-rare (popmax 0.078%, nfe).

How common is BLTP2 p.Phe1091Leu (c.3271T>C) in the general population?

BLTP2 p.Phe1091Leu (c.3271T>C) is ultra-rare (popmax 0.078%, nfe) (gnomAD).

What do computational predictors say about BLTP2 p.Phe1091Leu (c.3271T>C)?

AlphaMissense predicts ambiguous (score 0.4174) — an in-silico prediction, not a clinical call.

BLTP2 p.Phe1091Leu

c.3271T>C · rs150753528 · VCV3134299

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4174 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.078%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4174	ambiguous
REVEL	0.127	moderately benign-leaning
SaProt	LLR -3.67	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 1,422 bp · p 0.43 · regional, not allelic
Overall
CADD	22.2	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 0.078% European (non-Finnish) · 920/1,179,572 alleles

Filtering AF 0.0738% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0721%

Overall 0.0609% 983/1,613,466 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.078%	1,282
Remaining individualsnot grpmax-eligible	0.0544%	1,838
Admixed American	0.02%	4,997
African / African-American	0.016%	6,252
Finnishnot grpmax-eligible	0.00469%	21,333
East Asian	0.00223%	44,848
South Asian	0.0011%	91,026

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.Phe1091Leu
Coding: c.3271T>C
MANE Select: NM_014680
dbSNP: rs150753528
Type: single nucleotide variant
Location: chr17:28633743 (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-phe1091leu (accessed [today's date]).

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