Is RAF1 p.Lys575= (c.1725G>A) pathogenic?

RAF1 p.Lys575= (c.1725G>A) is classified Likely benign in RAF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-28). Absent from gnomAD v4.1; Associated with RASopathy.

What condition is associated with RAF1 p.Lys575= (c.1725G>A)?

RAF1 p.Lys575= (c.1725G>A) is associated with RASopathy (ClinVar).

How common is RAF1 p.Lys575= (c.1725G>A) in the general population?

RAF1 p.Lys575= (c.1725G>A) is absent from gnomAD v4.1 (gnomAD).

RAF1 p.Lys575=

c.1725G>A · rs747395643 · VCV1910939

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 1.1	GERP -1.4, phastCons 1
Overall
CADD	9.363	PHRED · no single calibrated threshold — expert panels disagree

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.Lys575=
Coding: c.1725G>A
MANE Select: NM_002880
dbSNP: rs747395643
Type: single nucleotide variant
Location: chr3:12584925 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.24 · 76 PDB
Residue 575: a β-strand; 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.Lys575Asn Uncertain significance ★ ⚠ same residue
RAF1 p.Lys575Thr Uncertain significance ★ ⚠ 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-lys575 (accessed [today's date]).

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