Is RAF1 p.Pro600Arg (c.1799C>G) pathogenic?

RAF1 p.Pro600Arg (c.1799C>G) is classified Uncertain significance in RAF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-20). AlphaMissense: likely pathogenic (0.8716); Absent from gnomAD v4.1; Associated with RASopathy.

What condition is associated with RAF1 p.Pro600Arg (c.1799C>G)?

RAF1 p.Pro600Arg (c.1799C>G) is associated with RASopathy (ClinVar).

How common is RAF1 p.Pro600Arg (c.1799C>G) in the general population?

RAF1 p.Pro600Arg (c.1799C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RAF1 p.Pro600Arg (c.1799C>G)?

AlphaMissense predicts likely pathogenic (score 0.8716) — an in-silico prediction, not a clinical call.

RAF1 p.Pro600Arg

c.1799C>G · rs143037121 · VCV2100649

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8716 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

RASopathy

Computational evidence

Protein change
AlphaMissense	0.8716	likely pathogenic
REVEL	0.627	indeterminate
SaProt	LLR -9.91	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1
Overall
CADD	29.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RAF1
Protein: p.Pro600Arg
Coding: c.1799C>G
MANE Select: NM_002880
dbSNP: rs143037121
Type: single nucleotide variant
Location: chr3:12584851 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.24 · 76 PDB
Residue 600: an α-helix; the protein kinase domain

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.Pro600His Uncertain significance ★★ ⚠ same residue
RAF1 p.Pro600= Likely benign ★★ 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-pro600arg (accessed [today's date]).

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