Is BRAF p.Gln709Glu (c.2125C>G) pathogenic?

BRAF p.Gln709Glu (c.2125C>G) is classified Pathogenic in BRAF (ClinVar, Single submitter, 1 submitter; last evaluated 2019-11-18). AlphaMissense: likely benign (0.3269); Absent from gnomAD v4.1.

How common is BRAF p.Gln709Glu (c.2125C>G) in the general population?

BRAF p.Gln709Glu (c.2125C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRAF p.Gln709Glu (c.2125C>G)?

AlphaMissense predicts likely benign (score 0.3269) — an in-silico prediction, not a clinical call.

BRAF p.Gln709Glu

c.2125C>G · rs1554389828 · VCV1210729

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3269 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3269	likely benign ⚠ discordant with ClinVar
REVEL	0.631	indeterminate
SaProt	LLR -7.87	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 4, phastCons 1
Overall
CADD	27.5	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.Gln709Glu
Coding: c.2125C>G
MANE Select: NM_004333
dbSNP: rs1554389828
Type: single nucleotide variant
Location: chr7:140739814 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.87 · 135 PDB
Residue 709: an α-helix; the protein kinase domain; a UniProt-annotated variant site (in cfc1)

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

Similar variants

BRAF p.Gln709Arg Pathogenic ★ same residue
BRAF p.Gln709Lys Uncertain significance ★ ⚠ same residue
BRAF p.Ala246Pro Pathogenic ★★★ same type
BRAF p.Asn581Asp Pathogenic ★★★ same type
BRAF p.Asp594Val Pathogenic ★★★ same type
BRAF p.Cys532Tyr Likely pathogenic ★★★ same type
BRAF p.Gln257Arg Pathogenic ★★★ same type
BRAF p.Gly265Arg Likely pathogenic ★★★ same type

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-gln709glu (accessed [today's date]).

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