Is BRAF p.Gly30Asp (c.89G>A) pathogenic?

BRAF p.Gly30Asp (c.89G>A) is classified Uncertain significance in BRAF (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-29). AlphaMissense: likely benign (0.1754); Very rare (popmax 0.00277%, afr); Associated with RASopathy.

What condition is associated with BRAF p.Gly30Asp (c.89G>A)?

BRAF p.Gly30Asp (c.89G>A) is associated with RASopathy, cardiofaciocutaneous syndrome 1, Noonan syndrome with multiple lentigines (ClinVar).

How common is BRAF p.Gly30Asp (c.89G>A) in the general population?

BRAF p.Gly30Asp (c.89G>A) is very rare (popmax 0.00277%, afr) (gnomAD).

What do computational predictors say about BRAF p.Gly30Asp (c.89G>A)?

AlphaMissense predicts likely benign (score 0.1754) — an in-silico prediction, not a clinical call.

BRAF p.Gly30Asp

c.89G>A · rs1273585752 · VCV666414

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1754 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00277%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

RASopathy

Computational evidence

Protein change
AlphaMissense	0.1754	likely benign
REVEL	0.205	benign-leaning
SaProt	LLR -10.99	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 1.3, phastCons 1
Overall
CADD	21.1	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 0.00277% African / African-American · 2/72,178 alleles

Filtering AF 0.00046% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000172%

Overall 0.00072% 11/1,526,764 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00457%	21,905
Remaining individualsnot grpmax-eligible	0.00336%	29,733
African / African-Americangrpmax	0.00277%	36,089
East Asian	0.00247%	40,436
South Asian	0.00119%	83,740
European (non-Finnish)	0.000262%	380,989

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Gly30Asp
Coding: c.89G>A
MANE Select: NM_004333
dbSNP: rs1273585752
Type: single nucleotide variant
Location: chr7:140924615 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.87 · 135 PDB
Residue 30: 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

Also linked: cardiofaciocutaneous syndrome 1 Noonan syndrome with multiple lentigines

Similar variants

BRAF p.Gly30= Likely benign ★★ same residue
BRAF p.Gly30Ala Uncertain significance ★ ⚠ same residue
BRAF p.Gly30Cys Uncertain significance ★ ⚠ same residue
BRAF p.Gly30Ser Uncertain significance ★ ⚠ same residue
BRAF p.Gly30Val Uncertain significance ★★ ⚠ same residue
BRAF p.Ala246Pro Pathogenic ★★★ same condition
BRAF p.Asn581Asp Pathogenic ★★★ same condition
BRAF p.Asp594Val 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-gly30asp (accessed [today's date]).

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