Is BRAF p.Asn368Ser (c.1103A>G) pathogenic?

BRAF p.Asn368Ser (c.1103A>G) is classified Uncertain significance in BRAF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-13). AlphaMissense: likely pathogenic (0.7619); Very rare (popmax 0.0011%, sas); Associated with RASopathy.

What condition is associated with BRAF p.Asn368Ser (c.1103A>G)?

BRAF p.Asn368Ser (c.1103A>G) is associated with RASopathy (ClinVar).

How common is BRAF p.Asn368Ser (c.1103A>G) in the general population?

BRAF p.Asn368Ser (c.1103A>G) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about BRAF p.Asn368Ser (c.1103A>G)?

AlphaMissense predicts likely pathogenic (score 0.7619) — an in-silico prediction, not a clinical call.

BRAF p.Asn368Ser

c.1103A>G · rs1802300066 · VCV1013818

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7619 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

RASopathy

Computational evidence

Protein change
AlphaMissense	0.7619	likely pathogenic
REVEL	0.381	indeterminate
SaProt	LLR -6.67	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 3.5, phastCons 1
Overall
CADD	24.5	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 0.0011% South Asian · 1/91,088 alleles

Overall 0.000137% 2/1,461,844 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,088
European (non-Finnish)	8.47e-05%	1,180,018

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.Asn368Ser
Coding: c.1103A>G
MANE Select: NM_004333
dbSNP: rs1802300066
Type: single nucleotide variant
Location: chr7:140794345 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.87 · 135 PDB
Residue 368: an α-helix; the 'disordered' region

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

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-asn368ser (accessed [today's date]).

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