Is BGN p.Val49Phe (c.145G>T) pathogenic?

BGN p.Val49Phe (c.145G>T) is classified Uncertain significance in BGN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-01). AlphaMissense: likely benign (0.0607); Very rare (popmax 8.25e-05%).

How common is BGN p.Val49Phe (c.145G>T) in the general population?

BGN p.Val49Phe (c.145G>T) is very rare (popmax 8.25e-05%) (gnomAD).

What do computational predictors say about BGN p.Val49Phe (c.145G>T)?

AlphaMissense predicts likely benign (score 0.0607) — an in-silico prediction, not a clinical call.

BGN p.Val49Phe

c.145G>T · VCV4803562

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0607 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.25e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0607	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -6.23	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 1.1	GERP -3.4, phastCons 0.29
Regional constraint	o/e 0.94	unconstrained · MANE · 3,810 bp · p 0.25 · regional, not allelic
Overall
CADD	0.524	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 8.25e-05%

Overall 8.25e-05% 1/1,211,764 alleles · very rare exomes 1/1,097,825 · genomes 0/113,939 · joint denominator

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: BGN
Protein: p.Val49Phe
Coding: c.145G>T
MANE Select: NM_001711
Type: single nucleotide variant
Location: chrX:153504776 (GRCh38)
Structure: AlphaFold pLDDT 85.72

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

Similar variants

BGN p.Val49Ile Uncertain significance ★★ ⚠ same residue
BGN c.770+1G>A Likely pathogenic ★★ same type
BGN p.Gln75Ter Pathogenic/Likely pathogenic ★★ same type
BGN p.Trp25Ter Likely pathogenic ★★ same type
BGN c.909+4A>G Uncertain significance ★★ same type
BGN p.Ala330Asp Uncertain significance ★★ ⚠ same type
BGN p.Ala330Pro Uncertain significance ★★ ⚠ same type
BGN p.Ala41Ser 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/bgn-p-val49phe (accessed [today's date]).

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