Is FOSB p.Asp181Glu (c.543C>A) pathogenic?

FOSB p.Asp181Glu (c.543C>A) is classified Uncertain significance in FOSB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-30). AlphaMissense: likely pathogenic (0.7997); Absent from gnomAD v4.1.

How common is FOSB p.Asp181Glu (c.543C>A) in the general population?

FOSB p.Asp181Glu (c.543C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FOSB p.Asp181Glu (c.543C>A)?

AlphaMissense predicts likely pathogenic (score 0.7997) — an in-silico prediction, not a clinical call.

FOSB p.Asp181Glu

c.543C>A · VCV4669289

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7997 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,562,516)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7997	likely pathogenic
REVEL	0.114	moderately benign-leaning
SaProt	LLR -10.00	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.007	GERP -3, phastCons 0.61
Regional constraint	o/e 0.42	unconstrained · MANE · 1,441 bp · p 1.1e-07 · regional, not allelic
Overall
CADD	19.85	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

No allele count reported in gnomAD v4.1 (AN 1,562,516). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: FOSB
Protein: p.Asp181Glu
Coding: c.543C>A
MANE Select: NM_006732
Type: single nucleotide variant
Location: chr19:45471289 (GRCh38)
Gene constraint: LOEUF 0.534 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 60.79 · 12 PDB
Residue 181: the bzip domain; an α-helix; the 'disordered' region; the 'basic motif' region

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

Similar variants

FOSB p.Asp181Asn Uncertain significance ★ ⚠ same residue
FOSB p.Asp181His Uncertain significance ★ ⚠ same residue
FOSB p.Pro220= Likely benign ★★ same type
FOSB p.Ala313Thr Uncertain significance ★ ⚠ same type
FOSB p.Ala313Val Uncertain significance ★ ⚠ same type
FOSB p.Ala337Thr Uncertain significance ★ ⚠ same type
FOSB p.Arg139Gln Uncertain significance ★ ⚠ same type
FOSB p.Arg139Gly 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/fosb-p-asp181glu (accessed [today's date]).

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