Is FOSB p.Ser130Arg (c.390T>G) pathogenic?

FOSB p.Ser130Arg (c.390T>G) is classified Uncertain significance in FOSB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-28). AlphaMissense: likely pathogenic (0.6377); Ultra-rare (popmax 0.0299%, nfe).

How common is FOSB p.Ser130Arg (c.390T>G) in the general population?

FOSB p.Ser130Arg (c.390T>G) is ultra-rare (popmax 0.0299%, nfe) (gnomAD).

What do computational predictors say about FOSB p.Ser130Arg (c.390T>G)?

AlphaMissense predicts likely pathogenic (score 0.6377) — an in-silico prediction, not a clinical call.

FOSB p.Ser130Arg

c.390T>G · rs201193101 · VCV2362533

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6377 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0299%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6377	likely pathogenic
REVEL	0.057	moderately benign-leaning
SaProt	LLR -8.40	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.7	GERP -3
Regional constraint	o/e 0.93	unconstrained · MANE · 2,362 bp · p 0.33 · regional, not allelic
Overall
CADD	4.646	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

Grpmax group 0.0299% European (non-Finnish) · 353/1,179,988 alleles

Filtering AF 0.0273% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0263%

Overall 0.0226% 365/1,613,610 alleles · ultra-rare exomes 342/1,461,584 · genomes 23/152,026 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0299%	3,343
Remaining individualsnot grpmax-eligible	0.0096%	10,414
African / African-American	0.00668%	14,972
Finnishnot grpmax-eligible	0.00157%	63,732

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: FOSB
Protein: p.Ser130Arg
Coding: c.390T>G
MANE Select: NM_006732
dbSNP: rs201193101
Type: single nucleotide variant
Location: chr19:45470892 (GRCh38)
Gene constraint: LOEUF 0.534 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 60.79 · 12 PDB
Residue 130: the 'disordered' region

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

Similar variants

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
FOSB p.Asp181Asn Uncertain significance ★ ⚠ same type
FOSB p.Asp181Glu 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-ser130arg (accessed [today's date]).

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