Is BRAF p.28GA[5] (c.83GCGCCG[5]) pathogenic?

BRAF p.28GA[5] (c.83GCGCCG[5]) is classified Uncertain significance in BRAF (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-11). Very rare (popmax 8.74e-05%, nfe); Associated with RASopathy.

What condition is associated with BRAF p.28GA[5] (c.83GCGCCG[5])?

BRAF p.28GA[5] (c.83GCGCCG[5]) is associated with RASopathy (ClinVar).

How common is BRAF p.28GA[5] (c.83GCGCCG[5]) in the general population?

BRAF p.28GA[5] (c.83GCGCCG[5]) is very rare (popmax 8.74e-05%, nfe) (gnomAD).

BRAF p.28GA[5]

c.83GCGCCG[5] · rs397507458 · VCV412321

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 8.74e-05%, nfe)

Conditions

RASopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.4	GERP 1.7, phastCons 1
Region caveats
Repeat context	tandem	(CGGCGC)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.74e-05% European (non-Finnish) · 1/1,144,228 alleles

Overall 7.26e-05% 1/1,377,378 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.28GA[5]
Coding: c.83GCGCCG[5]
MANE Select: NM_004333
dbSNP: rs397507458
Type: Microsatellite
Location: chr7:140924603 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.87 · 135 PDB

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.Ser127del Uncertain significance ★★ same condition
BRAF c.1432+17_1432+19del Benign/Likely benign ★★ same condition
BRAF c.2128-27_2128-18del Benign/Likely benign ★★ same condition
BRAF p.28GA[1] Conflicting classifications of pathogenicity ★ same condition
BRAF p.28GA[2] Conflicting classifications of pathogenicity ★ same condition
BRAF p.28GA[4] Conflicting classifications of pathogenicity ★ same condition
BRAF p.Gly10_Gly11dup Uncertain significance ★ same condition
BRAF c.2128-6_2128-5insTTTTTTTTTC Likely benign ★ 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-28ga-5 (accessed [today's date]).

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