Is RAF1 p.Ser285= (c.855C>T) pathogenic?

RAF1 p.Ser285= (c.855C>T) is classified Likely benign in RAF1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-29). Very rare (popmax 0.00833%, amr); Associated with Cardiovascular phenotype.

What condition is associated with RAF1 p.Ser285= (c.855C>T)?

RAF1 p.Ser285= (c.855C>T) is associated with Cardiovascular phenotype, RASopathy (ClinVar).

How common is RAF1 p.Ser285= (c.855C>T) in the general population?

RAF1 p.Ser285= (c.855C>T) is very rare (popmax 0.00833%, amr) (gnomAD).

RAF1 p.Ser285=

c.855C>T · rs763657486 · VCV518979

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.89	GERP -4.7, phastCons 0.99
Overall
CADD	9.866	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00833% Admixed American · 5/59,998 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00236%

Overall 0.00304% 49/1,614,018 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,000
European (non-Finnish)	0.00356%	28,096
Remaining individualsnot grpmax-eligible	0.0016%	62,490
South Asian	0.0011%	91,084

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: RAF1
Protein: p.Ser285=
Coding: c.855C>T
MANE Select: NM_002880
dbSNP: rs763657486
Type: single nucleotide variant
Location: chr3:12600395 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.24 · 76 PDB
Residue 285: the 'disordered' region

Full RAF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: RASopathy

Similar variants

RAF1 p.Ser285Arg Uncertain significance ★★ ⚠ same residue
RAF1 p.Ser285Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
RAF1 p.Arg256Ser Likely pathogenic ★★★ ⚠ same condition
RAF1 p.Gly361Ala Pathogenic ★★★ ⚠ same condition
RAF1 p.Leu613Val Pathogenic ★★★ same condition
RAF1 p.Pro261Ser Pathogenic ★★★ ⚠ same condition
RAF1 p.Ser257Leu Pathogenic ★★★ ⚠ same condition
RAF1 p.Ser257Pro Likely pathogenic ★★★ ⚠ same condition

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/raf1-p-ser285 (accessed [today's date]).

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