Is BRAF p.Glu26Asp (c.78G>T) pathogenic?

BRAF p.Glu26Asp (c.78G>T) is classified Benign/Likely benign in BRAF (ClinVar, Multiple submitters, 21 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.092); Low-frequency (popmax 3.47%, afr); Associated with Noonan syndrome and Noonan-related syndrome.

What condition is associated with BRAF p.Glu26Asp (c.78G>T)?

BRAF p.Glu26Asp (c.78G>T) is associated with Noonan syndrome and Noonan-related syndrome, cardiofaciocutaneous syndrome 1, Noonan syndrome 7 (ClinVar).

How common is BRAF p.Glu26Asp (c.78G>T) in the general population?

BRAF p.Glu26Asp (c.78G>T) is low-frequency (popmax 3.47%, afr) (gnomAD).

What do computational predictors say about BRAF p.Glu26Asp (c.78G>T)?

AlphaMissense predicts likely benign (score 0.092) — an in-silico prediction, not a clinical call.

BRAF p.Glu26Asp

c.78G>T · rs371877084 · VCV40337

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 21 submitters

AlphaMissense

likely benign

0.092 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.47%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Noonan syndrome and Noonan-related syndrome

Computational evidence

Protein change
AlphaMissense	0.092	likely benign
REVEL	0.168	moderately benign-leaning
SaProt	LLR -7.12	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1, phastCons 1
Overall
CADD	19.56	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

Grpmax group 3.47% African / African-American · 2,504/72,100 alleles

Filtering AF 3.36% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.31%

Overall 0.188% 2,863/1,519,096 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.47%	29
Admixed American	0.258%	388
Remaining individualsnot grpmax-eligible	0.206%	486
Middle Eastern	0.183%	547
European (non-Finnish)	0.00845%	11,831
South Asian	0.00359%	27,861

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.Glu26Asp
Coding: c.78G>T
MANE Select: NM_004333
dbSNP: rs371877084
Type: single nucleotide variant
Location: chr7:140924626 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.87 · 135 PDB
Residue 26: the 'disordered' region

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

Disease context

Noonan syndrome and Noonan-related syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiofaciocutaneous syndrome 1 Noonan syndrome 7 LEOPARD syndrome 3 Noonan syndrome RASopathy

Similar variants

BRAF p.Glu26Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
BRAF p.Glu26fs 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

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-glu26asp (accessed [today's date]).

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