Is FOS p.Arg287Cys (c.859C>T) pathogenic?

FOS p.Arg287Cys (c.859C>T) is classified Uncertain significance in FOS (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-16). AlphaMissense: likely benign (0.1521); Ultra-rare (popmax 0.0527%, sas).

How common is FOS p.Arg287Cys (c.859C>T) in the general population?

FOS p.Arg287Cys (c.859C>T) is ultra-rare (popmax 0.0527%, sas) (gnomAD).

What do computational predictors say about FOS p.Arg287Cys (c.859C>T)?

AlphaMissense predicts likely benign (score 0.1521) — an in-silico prediction, not a clinical call.

FOS p.Arg287Cys

c.859C>T · rs146332374 · VCV2232796

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1521 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0527%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1521	likely benign
REVEL	0.318	indeterminate
SaProt	LLR -5.12	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 2,438 bp · p 0.00036 · regional, not allelic
Overall
CADD	28.1	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 0.0527% South Asian · 48/91,092 alleles

Filtering AF 0.0437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0425%

Overall 0.0391% 630/1,609,786 alleles · ultra-rare exomes 595/1,457,574 · genomes 35/152,212 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0527%	1,898
European (non-Finnish)	0.047%	2,126
Remaining individualsnot grpmax-eligible	0.032%	3,123
Finnishnot grpmax-eligible	0.00669%	14,941
African / African-American	0.00267%	37,471
Admixed American	0.00167%	60,004

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.Arg287Cys
Coding: c.859C>T
MANE Select: NM_005252
dbSNP: rs146332374
Type: single nucleotide variant
Location: chr14:75281140 (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.Arg287His Uncertain significance ★ ⚠ same residue
FOS p.Lys176Asn Benign/Likely benign ★★ ⚠ same type
FOS p.Pro233= Likely benign ★★ same type
FOS p.Pro233Ala Likely benign ★★ same type
FOS p.Thr63= Benign ★★ same type
FOS p.Arg155Cys Likely pathogenic ★ same type
FOS p.Ala103Val Uncertain significance ★ ⚠ same type
FOS p.Ala184Asp 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-arg287cys (accessed [today's date]).

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