Is BRAF p.Lys483Ile (c.1448A>T) pathogenic?

BRAF p.Lys483Ile (c.1448A>T) is classified Likely pathogenic in BRAF (ClinVar, Single submitter, 1 submitter; last evaluated 2019-11-13). AlphaMissense: likely pathogenic (0.9999); Absent from gnomAD v4.1.

How common is BRAF p.Lys483Ile (c.1448A>T) in the general population?

BRAF p.Lys483Ile (c.1448A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRAF p.Lys483Ile (c.1448A>T)?

AlphaMissense predicts likely pathogenic (score 0.9999) — an in-silico prediction, not a clinical call.

BRAF p.Lys483Ile

c.1448A>T · rs1586126581 · VCV1198003

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic ✓ concordant with ClinVar · top 7% in BRAF
REVEL	0.952	strongly pathogenic-leaning
SaProt	LLR -13.37	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 6.8, phastCons 1
Overall
CADD	33.0	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.Lys483Ile
Coding: c.1448A>T
MANE Select: NM_004333
dbSNP: rs1586126581
Type: single nucleotide variant
Location: chr7:140778060 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.87 · 135 PDB
Residue 483: a β-strand; a binding site; the protein kinase domain

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

Similar variants

BRAF p.Lys483Gln Pathogenic/Likely pathogenic ★★ same residue
BRAF p.Lys483Thr Pathogenic ★ same residue
BRAF p.Lys483Arg Uncertain significance ★ ⚠ same residue
BRAF p.Lys483Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
BRAF p.Lys483Glu Uncertain significance ★ ⚠ same residue
BRAF p.Lys483= Likely benign ★ same residue
BRAF p.Ala246Pro Pathogenic ★★★ same type
BRAF p.Asn581Asp 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-lys483ile (accessed [today's date]).

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