Is BRAF p.Ser607Phe (c.1820C>T) pathogenic?

BRAF p.Ser607Phe (c.1820C>T) is classified Uncertain significance in BRAF (ClinVar, Expert panel, 4 submitters; last evaluated 2026-02-11). AlphaMissense: likely pathogenic (0.956); Very rare (popmax 8.48e-05%, nfe); Associated with RASopathy.

What condition is associated with BRAF p.Ser607Phe (c.1820C>T)?

BRAF p.Ser607Phe (c.1820C>T) is associated with RASopathy, cardiofaciocutaneous syndrome 1 (ClinVar).

How common is BRAF p.Ser607Phe (c.1820C>T) in the general population?

BRAF p.Ser607Phe (c.1820C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about BRAF p.Ser607Phe (c.1820C>T)?

AlphaMissense predicts likely pathogenic (score 0.956) — an in-silico prediction, not a clinical call.

BRAF p.Ser607Phe

c.1820C>T · rs1255101216 · VCV977327

Uncertain significance Expert panel

Classification

Uncertain significance

ClinVar

Review

Expert panel ★★★☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.956 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

RASopathy

Computational evidence

Protein change
AlphaMissense	0.956	likely pathogenic
REVEL	0.76	pathogenic-leaning
SaProt	LLR -12.44	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 6.8, phastCons 1
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.48e-05% European (non-Finnish) · 1/1,178,984 alleles

Overall 6.85e-05% 1/1,460,422 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: BRAF
Protein: p.Ser607Phe
Coding: c.1820C>T
MANE Select: NM_004333
dbSNP: rs1255101216
Type: single nucleotide variant
Location: chr7:140753315 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.87 · 135 PDB
Residue 607: a β-strand; the protein kinase domain

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

Also linked: cardiofaciocutaneous syndrome 1

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-ser607phe (accessed [today's date]).

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