Is BRAF p.Asp565Glu (c.1695T>A) pathogenic?

BRAF p.Asp565Glu (c.1695T>A) is classified Likely pathogenic in BRAF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-01). AlphaMissense: likely pathogenic (0.9665); Absent from gnomAD v4.1; Associated with RASopathy.

What condition is associated with BRAF p.Asp565Glu (c.1695T>A)?

BRAF p.Asp565Glu (c.1695T>A) is associated with RASopathy, cardiofaciocutaneous syndrome 1 (ClinVar).

How common is BRAF p.Asp565Glu (c.1695T>A) in the general population?

BRAF p.Asp565Glu (c.1695T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRAF p.Asp565Glu (c.1695T>A)?

AlphaMissense predicts likely pathogenic (score 0.9665) — an in-silico prediction, not a clinical call.

BRAF p.Asp565Glu

c.1695T>A · rs397507480 · VCV2769805

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9665 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

RASopathy

Computational evidence

Protein change
AlphaMissense	0.9665	likely pathogenic ✓ concordant with ClinVar
REVEL	0.564	indeterminate
SaProt	LLR -7.27	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.49	acceptor gain at this position · masked 0 · deltas
Constraint at this position
Conservation	phyloP 9.4	GERP 5.6, phastCons 1
Overall
CADD	25.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BRAF
Protein: p.Asp565Glu
Coding: c.1695T>A
MANE Select: NM_004333
dbSNP: rs397507480
Type: single nucleotide variant
Location: chr7:140754233 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.87 · 135 PDB
Residue 565: an α-helix; 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-asp565glu (accessed [today's date]).

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