Is RAF1 p.Ser352= (c.1056C>T) pathogenic?

RAF1 p.Ser352= (c.1056C>T) is classified Likely benign in RAF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-25). Very rare (popmax 0.00223%, eas); Associated with Cardiovascular phenotype.

What condition is associated with RAF1 p.Ser352= (c.1056C>T)?

RAF1 p.Ser352= (c.1056C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is RAF1 p.Ser352= (c.1056C>T) in the general population?

RAF1 p.Ser352= (c.1056C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

RAF1 p.Ser352=

c.1056C>T · rs1197498955 · VCV3222898

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 0.19	GERP 0.85, phastCons 0.88
Overall
CADD	10.84	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,882 alleles

Overall 0.000124% 2/1,614,080 alleles · very rare exomes 2/1,461,888 · genomes 0/152,192 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,882
South Asian	0.0011%	91,080

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.Ser352=
Coding: c.1056C>T
MANE Select: NM_002880
dbSNP: rs1197498955
Type: single nucleotide variant
Location: chr3:12599743 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.24 · 76 PDB
Residue 352: the protein kinase domain; a β-strand

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.Ser352Phe 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
RAF1 p.Ala566Thr 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-ser352 (accessed [today's date]).

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