Is RAF1 p.His230= (c.690C>T) pathogenic?

RAF1 p.His230= (c.690C>T) is classified Likely benign in RAF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-28). Very rare (popmax 8.47e-05%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with RAF1 p.His230= (c.690C>T)?

RAF1 p.His230= (c.690C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is RAF1 p.His230= (c.690C>T) in the general population?

RAF1 p.His230= (c.690C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

RAF1 p.His230=

c.690C>T · VCV4150066

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 5.3	GERP 1.9, phastCons 1
Overall
CADD	10.09	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,960 alleles

Overall 6.84e-05% 1/1,461,758 alleles · very rare

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.His230=
Coding: c.690C>T
MANE Select: NM_002880
Type: single nucleotide variant
Location: chr3:12604280 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.24 · 76 PDB
Residue 230: 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

Similar variants

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
RAF1 p.Ala566Thr Uncertain significance ★★ ⚠ same condition
RAF1 p.Ala7Gly 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-his230 (accessed [today's date]).

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