Is BRAF p.Gln417Arg (c.1250A>G) pathogenic?

BRAF p.Gln417Arg (c.1250A>G) is classified Uncertain significance in BRAF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-11). AlphaMissense: likely benign (0.2703); Very rare (popmax 0.00267%, afr); Associated with RASopathy.

What condition is associated with BRAF p.Gln417Arg (c.1250A>G)?

BRAF p.Gln417Arg (c.1250A>G) is associated with RASopathy (ClinVar).

How common is BRAF p.Gln417Arg (c.1250A>G) in the general population?

BRAF p.Gln417Arg (c.1250A>G) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about BRAF p.Gln417Arg (c.1250A>G)?

AlphaMissense predicts likely benign (score 0.2703) — an in-silico prediction, not a clinical call.

BRAF p.Gln417Arg

c.1250A>G · rs978365655 · VCV1935409

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2703 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

RASopathy

Computational evidence

Protein change
AlphaMissense	0.2703	likely benign
REVEL	0.317	indeterminate
SaProt	LLR -7.05	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 3.5, phastCons 1
Overall
CADD	24.9	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 0.00267% African / African-American · 2/74,910 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.00197% 3/152,186 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,455
European (non-Finnish)	8.47e-05%	1,180,011

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: BRAF
Protein: p.Gln417Arg
Coding: c.1250A>G
MANE Select: NM_004333
dbSNP: rs978365655
Type: single nucleotide variant
Location: chr7:140783085 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.87 · 135 PDB
Residue 417: the 'disordered' region

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

Disease context

RASopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BRAF p.Ala246Pro Pathogenic ★★★ same condition
BRAF p.Asn581Asp Pathogenic ★★★ same condition
BRAF p.Asp594Val Pathogenic ★★★ same condition
BRAF p.Cys532Tyr Likely pathogenic ★★★ same condition
BRAF p.Gln257Arg Pathogenic ★★★ same condition
BRAF p.Gly265Arg Likely pathogenic ★★★ same condition
BRAF p.Gly464Glu Pathogenic ★★★ same condition
BRAF p.Gly469Glu Pathogenic ★★★ 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/braf-p-gln417arg (accessed [today's date]).

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