Is BLTP3B p.Arg762Gln (c.2285G>A) pathogenic?

BLTP3B p.Arg762Gln (c.2285G>A) is classified Uncertain significance in BLTP3B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-11). AlphaMissense: likely benign (0.1659); Ultra-rare (popmax 0.0165%, mid).

How common is BLTP3B p.Arg762Gln (c.2285G>A) in the general population?

BLTP3B p.Arg762Gln (c.2285G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about BLTP3B p.Arg762Gln (c.2285G>A)?

AlphaMissense predicts likely benign (score 0.1659) — an in-silico prediction, not a clinical call.

BLTP3B p.Arg762Gln

c.2285G>A · rs765722745 · VCV2536095

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1659 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1659	likely benign
REVEL	0.33	indeterminate
SaProt	LLR -6.31	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 51 kb · p 0.37 · regional, not allelic
Overall
CADD	24.1	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 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000479% 7/1,461,830 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0032%	31,253
East Asian	0.00223%	44,890
African / African-American	0.00133%	75,054
European (non-Finnish)	0.000169%	589,988

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: BLTP3B
Protein: p.Arg762Gln
Coding: c.2285G>A
MANE Select: NM_015054
dbSNP: rs765722745
Type: single nucleotide variant
Location: chr12:100058992 (GRCh38)
Structure: AlphaFold pLDDT 67.53

Full BLTP3B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BLTP3B p.Leu491= Benign ★★ same type
BLTP3B p.Ala109Val Uncertain significance ★ ⚠ same type
BLTP3B p.Ala1162Thr Uncertain significance ★ ⚠ same type
BLTP3B p.Ala1272Ser Uncertain significance ★ ⚠ same type
BLTP3B p.Ala231Ser Uncertain significance ★ ⚠ same type
BLTP3B p.Ala231Thr Uncertain significance ★ ⚠ same type
BLTP3B p.Ala257Gly Uncertain significance ★ ⚠ same type
BLTP3B p.Ala66Thr 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/bltp3b-p-arg762gln (accessed [today's date]).

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