Is BRAF p.Ser37= (c.111G>A) pathogenic?

BRAF p.Ser37= (c.111G>A) is classified Likely benign in BRAF (ClinVar, Expert panel, 7 submitters; last evaluated 2017-04-03). Very rare (popmax 0.00276%, afr); Associated with RASopathy.

What condition is associated with BRAF p.Ser37= (c.111G>A)?

BRAF p.Ser37= (c.111G>A) is associated with RASopathy (ClinVar).

How common is BRAF p.Ser37= (c.111G>A) in the general population?

BRAF p.Ser37= (c.111G>A) is very rare (popmax 0.00276%, afr) (gnomAD).

BRAF p.Ser37=

c.111G>A · rs727502906 · VCV162804

Likely benign Expert panel

Classification

Likely benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00276%, afr)

Conditions

RASopathy

ClinGen expert panel — RASopathy VCEP

Likely Benign for RASopathy. Applied ACMG criteria (verbatim):

BP5 BP7

Curation rationale (ClinGen, verbatim)

The c.111G>A (p.Ser37=) variant in BRAF is a synonymous (silent) variant at a nucleotide that is not highly conserved and is not predicted to impact splicing (BP7). This variant has been identified in a patient with an alternate molecular basis for disease (BP5; Partners LMM, GeneDx internal data, GTR ID's: SCV000197179.4, SCV000512270.5). In summary, this variant meets criteria to be classified as likely benign. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): BP7, BP5.

ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.

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 0.72	GERP 1.5, phastCons 1
Overall
CADD	13.19	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00276% African / African-American · 2/72,530 alleles

Filtering AF 0.00186% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.00209% 32/1,529,722 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00276%	36,265
European (non-Finnish)	0.00262%	38,151

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.Ser37=
Coding: c.111G>A
MANE Select: NM_004333
dbSNP: rs727502906
Type: single nucleotide variant
Location: chr7:140924593 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.87 · 135 PDB
Residue 37: 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.Ser37Leu Uncertain significance ★ ⚠ same residue
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

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-ser37 (accessed [today's date]).

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