Is BRAF p.Asn581Ser (c.1742A>G) pathogenic?

BRAF p.Asn581Ser (c.1742A>G) is classified Likely pathogenic in BRAF (ClinVar, Single submitter, 3 submitters; last evaluated 2013-07-19). AlphaMissense: likely pathogenic (0.6791); Very rare (popmax 0.000175%, nfe); Associated with non-small cell lung carcinoma.

What condition is associated with BRAF p.Asn581Ser (c.1742A>G)?

BRAF p.Asn581Ser (c.1742A>G) is associated with non-small cell lung carcinoma, lung adenocarcinoma (ClinVar).

How common is BRAF p.Asn581Ser (c.1742A>G) in the general population?

BRAF p.Asn581Ser (c.1742A>G) is very rare (popmax 0.000175%, nfe) (gnomAD).

What do computational predictors say about BRAF p.Asn581Ser (c.1742A>G)?

AlphaMissense predicts likely pathogenic (score 0.6791) — an in-silico prediction, not a clinical call.

BRAF p.Asn581Ser

c.1742A>G · rs121913370 · VCV177776

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.6791 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000175%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

non-small cell lung carcinoma

Computational evidence

Protein change
AlphaMissense	0.6791	likely pathogenic ✓ concordant with ClinVar
REVEL	0.907	moderately pathogenic-leaning
SaProt	LLR -14.07	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.33	acceptor gain at this position · masked 0 · deltas
Constraint at this position
Conservation	phyloP 7.9	GERP 6.8, phastCons 1
Overall
CADD	29.5	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

Grpmax group 0.000175% European (non-Finnish) · 2/1,143,670 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000141% 2/1,421,494 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.

Cancer therapy — CIViC

Disease	Therapies	Level	Significance
Cancer	Vemurafenib	C	Sensitivity/Response

Variant & gene context

Gene: BRAF
Protein: p.Asn581Ser
Coding: c.1742A>G
MANE Select: NM_004333
dbSNP: rs121913370
Type: single nucleotide variant
Location: chr7:140753393 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.87 · 135 PDB
Residue 581: an α-helix; the protein kinase domain; a UniProt-annotated variant site (in cfc1); a UniProt-annotated variant site (in a colorectal adenocarcinoma sample; somatic mutation)

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

Disease context

non-small cell lung carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: lung adenocarcinoma

Similar variants

BRAF p.Asn581Asp Pathogenic ★★★ same residue
BRAF p.Asn581Lys Pathogenic/Likely pathogenic ★★ same residue
BRAF p.Asn581His Conflicting classifications of pathogenicity ★ ⚠ same residue
BRAF p.Asn581Ile Uncertain significance ★ ⚠ same residue
BRAF p.Asn581Thr Uncertain significance ⚠ same residue
BRAF p.Gly464Val Pathogenic/Likely pathogenic ★★ same condition
BRAF p.Leu597Val Pathogenic ★★ same condition
BRAF p.Gly469Ala 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-asn581ser (accessed [today's date]).

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