Is RAF1 p.Ala237Asp (c.710C>A) pathogenic?

RAF1 p.Ala237Asp (c.710C>A) is classified Uncertain significance in RAF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-12). AlphaMissense: ambiguous (0.4488); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with RAF1 p.Ala237Asp (c.710C>A)?

RAF1 p.Ala237Asp (c.710C>A) is associated with Cardiovascular phenotype (ClinVar).

How common is RAF1 p.Ala237Asp (c.710C>A) in the general population?

RAF1 p.Ala237Asp (c.710C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RAF1 p.Ala237Asp (c.710C>A)?

AlphaMissense predicts ambiguous (score 0.4488) — an in-silico prediction, not a clinical call.

RAF1 p.Ala237Asp

c.710C>A · VCV4150069

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4488 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.4488	ambiguous
REVEL	0.302	indeterminate
SaProt	LLR -4.72	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 1.9, phastCons 1
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

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

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.Ala237Asp
Coding: c.710C>A
MANE Select: NM_002880
Type: single nucleotide variant
Location: chr3:12604260 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.24 · 76 PDB
Residue 237: the 'disordered' region; a UniProt-annotated variant site (in cmd1nn; shows a mild increase in kinase activity)

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.Ala237Thr Uncertain significance ★★ ⚠ same residue
RAF1 p.Ala237Gly Uncertain significance ★ ⚠ same residue
RAF1 p.Ala237Val 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

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-ala237asp (accessed [today's date]).

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