Is RAF1 p.His79Arg (c.236A>G) pathogenic?

RAF1 p.His79Arg (c.236A>G) is classified Uncertain significance in RAF1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2020-06-11). AlphaMissense: likely benign (0.0939); Very rare (popmax 0.000424%, nfe); Associated with dilated cardiomyopathy 1NN.

What condition is associated with RAF1 p.His79Arg (c.236A>G)?

RAF1 p.His79Arg (c.236A>G) is associated with dilated cardiomyopathy 1NN (ClinVar).

How common is RAF1 p.His79Arg (c.236A>G) in the general population?

RAF1 p.His79Arg (c.236A>G) is very rare (popmax 0.000424%, nfe) (gnomAD).

How is Familial isolated dilated cardiomyopathy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about RAF1 p.His79Arg (c.236A>G)?

AlphaMissense predicts likely benign (score 0.0939) — an in-silico prediction, not a clinical call.

RAF1 p.His79Arg

c.236A>G · rs1387880716 · VCV624212

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0939 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dilated cardiomyopathy 1NN

Computational evidence

Protein change
AlphaMissense	0.0939	likely benign
REVEL	0.119	moderately benign-leaning
SaProt	LLR -3.59	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.6, phastCons 1
Overall
CADD	17.91	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,180,014 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000342% 5/1,461,874 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.His79Arg
Coding: c.236A>G
MANE Select: NM_002880
dbSNP: rs1387880716
Type: single nucleotide variant
Location: chr3:12612034 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.24 · 76 PDB
Residue 79: the rbd domain; an α-helix

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

Disease context

dilated cardiomyopathy 1NN — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial isolated dilated cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

RAF1 p.His79= Likely benign ★★ same residue
RAF1 p.His79Gln Uncertain significance ★ ⚠ same residue
RAF1 p.Ser257Leu Pathogenic ★★★ ⚠ same condition
RAF1 p.Arg398Leu Uncertain significance ★★★ ⚠ same condition
RAF1 c.581+4A>G Likely benign ★★★ same condition
RAF1 c.-204G>C Benign ★★★ same condition
RAF1 p.Ala42Thr Likely benign ★★★ same condition
RAF1 p.Asp371= Likely benign ★★★ 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-his79arg (accessed [today's date]).

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