Is FOS p.Thr63= (c.189G>A) pathogenic?

FOS p.Thr63= (c.189G>A) is classified Benign in FOS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-12-31). Common (popmax 7.57%, afr) — too common for a highly-penetrant pathogenic allele.

FOS p.Thr63=

Q: How common is FOS p.Thr63= (c.189G>A) in the general population?

FOS p.Thr63= (c.189G>A) is common (popmax 7.57%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.189G>A · rs76195634 · VCV720688

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 7.57%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.048	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.54	GERP -3.5, phastCons 0.004
Overall
CADD	8.183	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.57% African / African-American · 5,682/75,016 alleles

Filtering AF 7.41% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.34%

Overall 0.393% 6,342/1,613,634 alleles · common exomes 3,147/1,461,418 · genomes 3,195/152,216 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.57%	13
Remaining individualsnot grpmax-eligible	0.49%	204
Admixed American	0.437%	229
Middle Eastern	0.149%	673
South Asian	0.0198%	5,058
European (non-Finnish)	0.00551%	18,150

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: FOS
Protein: p.Thr63=
Coding: c.189G>A
MANE Select: NM_005252
dbSNP: rs76195634
Type: single nucleotide variant
Location: chr14:75279924 (GRCh38)
Gene constraint: LOEUF 0.581 · pLI 0.87 (gnomAD)
Structure: AlphaFold pLDDT 58.48 · 3 PDB

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

Similar variants

FOS p.Lys176Asn Benign/Likely benign ★★ ⚠ same type
FOS p.Pro233= Likely benign ★★ same type
FOS p.Pro233Ala Likely benign ★★ same type
FOS p.Arg155Cys Likely pathogenic ★ same type
FOS p.Ala103Val Uncertain significance ★ ⚠ same type
FOS p.Ala184Asp Uncertain significance ★ ⚠ same type
FOS p.Ala203Val Uncertain significance ★ ⚠ same type
FOS p.Arg108Gly 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/fos-p-thr63 (accessed [today's date]).

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