Is BLVRB p.Ile176Val (c.526A>G) pathogenic?

BLVRB p.Ile176Val (c.526A>G) is classified Uncertain significance in BLVRB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-06). AlphaMissense: likely benign (0.3271); Very rare (popmax 0.00415%, nfe).

How common is BLVRB p.Ile176Val (c.526A>G) in the general population?

BLVRB p.Ile176Val (c.526A>G) is very rare (popmax 0.00415%, nfe) (gnomAD).

What do computational predictors say about BLVRB p.Ile176Val (c.526A>G)?

AlphaMissense predicts likely benign (score 0.3271) — an in-silico prediction, not a clinical call.

BLVRB p.Ile176Val

c.526A>G · rs368720101 · VCV2367460

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3271 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00415%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3271	likely benign
REVEL	0.24	benign-leaning
SaProt	LLR -8.77	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 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 18 kb · p 0.6 · regional, not allelic
Overall
CADD	25.5	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 0.00415% European (non-Finnish) · 49/1,180,018 alleles

Filtering AF 0.00318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00286%

Overall 0.00304% 49/1,614,020 alleles · very rare

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: BLVRB
Protein: p.Ile176Val
Coding: c.526A>G
MANE Select: NM_000713
dbSNP: rs368720101
Type: single nucleotide variant
Location: chr19:40447984 (GRCh38)
Gene constraint: LOEUF 1.718 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.71 · 23 PDB
Residue 176: a β-strand

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

Similar variants

BLVRB p.Arg140Gly Likely benign ★★ same type
BLVRB p.Arg46Gln Likely benign ★★ same type
BLVRB p.Thr84= Benign ★★ same type
BLVRB p.Ala162Val Uncertain significance ★ ⚠ same type
BLVRB p.Ala21Thr Uncertain significance ★ ⚠ same type
BLVRB p.Ala26Thr Uncertain significance ★ ⚠ same type
BLVRB p.Ala7Val Uncertain significance ★ ⚠ same type
BLVRB p.Ala91Thr 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/blvrb-p-ile176val (accessed [today's date]).

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