Is BLTP3B p.Pro1072Arg (c.3215C>G) pathogenic?

BLTP3B p.Pro1072Arg (c.3215C>G) is classified Uncertain significance in BLTP3B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-15). AlphaMissense: likely benign (0.0725); Very rare (popmax 0.0096%, afr).

How common is BLTP3B p.Pro1072Arg (c.3215C>G) in the general population?

BLTP3B p.Pro1072Arg (c.3215C>G) is very rare (popmax 0.0096%, afr) (gnomAD).

What do computational predictors say about BLTP3B p.Pro1072Arg (c.3215C>G)?

AlphaMissense predicts likely benign (score 0.0725) — an in-silico prediction, not a clinical call.

BLTP3B p.Pro1072Arg

c.3215C>G · rs550401137 · VCV3134416

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0725 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0096%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0725	likely benign
REVEL	0.108	moderately benign-leaning
SaProt	LLR -6.87	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 3.8	GERP 1.7, phastCons 0.73
Regional constraint	o/e 0.98	unconstrained · MANE · 51 kb · p 0.37 · regional, not allelic
Overall
CADD	10.07	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 0.0096% African / African-American · 7/72,934 alleles

Filtering AF 0.00448% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00316%

Overall 0.000695% 11/1,582,384 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0096%	10,419
Admixed American	0.004%	24,981
South Asian	0.00118%	84,670
European (non-Finnish)	8.54e-05%	1,171,506

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.Pro1072Arg
Coding: c.3215C>G
MANE Select: NM_015054
dbSNP: rs550401137
Type: single nucleotide variant
Location: chr12:100058062 (GRCh38)
Structure: AlphaFold pLDDT 67.53
Residue 1072: the 'disordered' region

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-pro1072arg (accessed [today's date]).

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