Is FGB p.Asp91Val (c.272A>T) pathogenic?

FGB p.Asp91Val (c.272A>T) is classified Uncertain significance in FGB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-16). AlphaMissense: likely benign (0.3296); Absent from gnomAD v4.1.

How common is FGB p.Asp91Val (c.272A>T) in the general population?

FGB p.Asp91Val (c.272A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FGB p.Asp91Val (c.272A>T)?

AlphaMissense predicts likely benign (score 0.3296) — an in-silico prediction, not a clinical call.

FGB p.Asp91Val

c.272A>T · VCV4525832

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3296 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3296	likely benign
REVEL	0.848	moderately pathogenic-leaning
SaProt	LLR -4.97	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 6,287 bp · p 0.13 · regional, not allelic
Overall
CADD	25.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FGB
Protein: p.Asp91Val
Coding: c.272A>T
MANE Select: NM_005141
Type: single nucleotide variant
Location: chr4:154565965 (GRCh38)
Gene constraint: LOEUF 0.662 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 84.43 · 41 PDB
Residue 91: a UniProt-annotated variant site (in new york-1)

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

Similar variants

FGB p.Arg44Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
FGB p.Arg47Ter Pathogenic/Likely pathogenic ★★ same type
FGB p.Arg199Cys Uncertain significance ★★ ⚠ same type
FGB p.Arg199His Uncertain significance ★★ ⚠ same type
FGB p.Arg224His Uncertain significance ★★ ⚠ same type
FGB p.Arg395Gly Uncertain significance ★★ ⚠ same type
FGB p.Arg47Gln Uncertain significance ★★ same type
FGB p.Arg74Leu 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/fgb-p-asp91val (accessed [today's date]).

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