Is BRAF p.Cys173Tyr (c.518G>A) pathogenic?

BRAF p.Cys173Tyr (c.518G>A) is classified Uncertain significance in BRAF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-21). AlphaMissense: ambiguous (0.4675); Very rare (popmax 0.000764%, nfe); Associated with BRAF-related disorder.

What condition is associated with BRAF p.Cys173Tyr (c.518G>A)?

BRAF p.Cys173Tyr (c.518G>A) is associated with BRAF-related disorder (ClinVar).

How common is BRAF p.Cys173Tyr (c.518G>A) in the general population?

BRAF p.Cys173Tyr (c.518G>A) is very rare (popmax 0.000764%, nfe) (gnomAD).

What do computational predictors say about BRAF p.Cys173Tyr (c.518G>A)?

AlphaMissense predicts ambiguous (score 0.4675) — an in-silico prediction, not a clinical call.

BRAF p.Cys173Tyr

c.518G>A · rs1411975481 · VCV2633057

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4675 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000764%, nfe)

Conditions

BRAF-related disorder

Computational evidence

Protein change
AlphaMissense	0.4675	ambiguous
REVEL	0.344	indeterminate
SaProt	LLR -6.44	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 3.6, phastCons 1
Overall
CADD	25.1	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 0.000764% European (non-Finnish) · 9/1,178,748 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000558% 9/1,612,098 alleles · very rare

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.Cys173Tyr
Coding: c.518G>A
MANE Select: NM_004333
dbSNP: rs1411975481
Type: single nucleotide variant
Location: chr7:140808982 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.87 · 135 PDB
Residue 173: the rbd domain

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

Disease context

BRAF-related disorder

Similar variants

BRAF p.Cys173Arg Uncertain significance ★★ ⚠ same residue
BRAF p.Cys173= Likely benign ★ same residue
BRAF p.Glu501Ala Pathogenic ★★ same condition
BRAF p.Lys601Gln Pathogenic ★★ same condition
BRAF p.Phe468Ser Pathogenic/Likely pathogenic ★★ same condition
BRAF p.Thr241Met Pathogenic/Likely pathogenic ★★ same condition
BRAF p.Trp531Arg Pathogenic/Likely pathogenic ★★ same condition
BRAF p.Trp531Leu 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-cys173tyr (accessed [today's date]).

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