Is RAF1 p.Phe387= (c.1161C>T) pathogenic?

RAF1 p.Phe387= (c.1161C>T) is classified Likely benign in RAF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-07). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with RAF1 p.Phe387= (c.1161C>T)?

RAF1 p.Phe387= (c.1161C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is RAF1 p.Phe387= (c.1161C>T) in the general population?

RAF1 p.Phe387= (c.1161C>T) is absent from gnomAD v4.1 (gnomAD).

RAF1 p.Phe387=

c.1161C>T · VCV4614802

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.69	GERP -4.6, phastCons 1
Overall
CADD	9.966	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.Phe387=
Coding: c.1161C>T
MANE Select: NM_002880
Type: single nucleotide variant
Location: chr3:12591740 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.24 · 76 PDB
Residue 387: an α-helix; the protein kinase domain

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

Similar variants

RAF1 p.Phe387Leu Uncertain significance ★ ⚠ same residue
RAF1 p.Phe387_Gln388delinsLeuGlu Uncertain significance ★ same residue
RAF1 p.Pro261His Pathogenic/Likely pathogenic ★★ ⚠ same condition
RAF1 p.Pro261Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
RAF1 c.207+5G>T Uncertain significance ★★ same condition
RAF1 c.834+4A>C Uncertain significance ★★ same condition
RAF1 c.-4A>C Uncertain significance ★★ same condition
RAF1 p.Ala119Val Uncertain significance ★★ ⚠ 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-phe387 (accessed [today's date]).

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