Is BLTP2 p.Arg960Cys (c.2878C>T) pathogenic?

BLTP2 p.Arg960Cys (c.2878C>T) is classified Uncertain significance in BLTP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-02). AlphaMissense: likely pathogenic (0.7332); Very rare (popmax 0.00667%, amr).

How common is BLTP2 p.Arg960Cys (c.2878C>T) in the general population?

BLTP2 p.Arg960Cys (c.2878C>T) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about BLTP2 p.Arg960Cys (c.2878C>T)?

AlphaMissense predicts likely pathogenic (score 0.7332) — an in-silico prediction, not a clinical call.

BLTP2 p.Arg960Cys

c.2878C>T · VCV3991810

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7332 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7332	likely pathogenic
REVEL	0.436	indeterminate
SaProt	LLR -4.66	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 1,422 bp · p 0.43 · regional, not allelic
Overall
CADD	29.5	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 0.00667% Admixed American · 4/60,008 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00198% 32/1,614,026 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	15,002
Remaining individualsnot grpmax-eligible	0.0048%	20,828
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
East Asian	0.00223%	44,880
European (non-Finnish)	0.00178%	56,192
African / African-American	0.00134%	74,902
South Asian	0.0011%	91,084

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.Arg960Cys
Coding: c.2878C>T
MANE Select: NM_014680
Type: single nucleotide variant
Location: chr17:28634709 (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.Ala248Thr Uncertain significance ★ ⚠ same type
BLTP2 p.Ala324Thr Uncertain significance ★ ⚠ same type
BLTP2 p.Ala393Thr Uncertain significance ★ ⚠ same type
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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-arg960cys (accessed [today's date]).

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