Is RAF1 p.Arg563= (c.1689A>G) pathogenic?

RAF1 p.Arg563= (c.1689A>G) is classified Likely benign in RAF1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-01). Very rare (popmax 0.00833%, amr); Associated with RASopathy.

What condition is associated with RAF1 p.Arg563= (c.1689A>G)?

RAF1 p.Arg563= (c.1689A>G) is associated with RASopathy (ClinVar).

How common is RAF1 p.Arg563= (c.1689A>G) in the general population?

RAF1 p.Arg563= (c.1689A>G) is very rare (popmax 0.00833%, amr) (gnomAD).

RAF1 p.Arg563=

c.1689A>G · rs1358420019 · VCV516880

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Conditions

RASopathy

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 -1.8	GERP -5.3
Overall
CADD	8.806	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00833% Admixed American · 5/60,002 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00031% 5/1,613,998 alleles · very rare exomes 4/1,461,866 · genomes 1/152,132 · joint denominator

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.Arg563=
Coding: c.1689A>G
MANE Select: NM_002880
dbSNP: rs1358420019
Type: single nucleotide variant
Location: chr3:12584961 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.24 · 76 PDB
Residue 563: an α-helix; the protein kinase domain; a modified residue (symmetric dimethylarginine; by prmt5)

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

Disease context

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

Similar variants

RAF1 p.Arg563Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
RAF1 p.Arg563Ter 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-arg563 (accessed [today's date]).

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