Is BRAF p.Ala34Val (c.101C>T) pathogenic?

BRAF p.Ala34Val (c.101C>T) is classified Likely benign in BRAF (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely benign (0.1068); Very rare (popmax 0.00276%, afr); Associated with Noonan syndrome.

What condition is associated with BRAF p.Ala34Val (c.101C>T)?

BRAF p.Ala34Val (c.101C>T) is associated with Noonan syndrome (ClinVar).

How common is BRAF p.Ala34Val (c.101C>T) in the general population?

BRAF p.Ala34Val (c.101C>T) is very rare (popmax 0.00276%, afr) (gnomAD).

What do computational predictors say about BRAF p.Ala34Val (c.101C>T)?

AlphaMissense predicts likely benign (score 0.1068) — an in-silico prediction, not a clinical call.

BRAF p.Ala34Val

c.101C>T · rs1424449802 · VCV666415

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1068 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00276%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Noonan syndrome

Computational evidence

Protein change
AlphaMissense	0.1068	likely benign
REVEL	0.167	moderately benign-leaning
SaProt	LLR -8.60	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.4	GERP 1.7, phastCons 1
Overall
CADD	23.3	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 0.00276% African / African-American · 2/72,390 alleles

Filtering AF 0.000458% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000172%

Overall 0.00132% 2/151,506 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.Ala34Val
Coding: c.101C>T
MANE Select: NM_004333
dbSNP: rs1424449802
Type: single nucleotide variant
Location: chr7:140924603 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.87 · 135 PDB
Residue 34: the 'disordered' region

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

Disease context

Noonan syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BRAF p.Ala34= Likely benign ★★ same residue
BRAF p.Ala34Gly Uncertain significance ★ ⚠ same residue
BRAF p.Ala246Pro Pathogenic ★★★ same condition
BRAF p.Gly265Arg Likely pathogenic ★★★ same condition
BRAF p.Gly464Glu Pathogenic ★★★ same condition
BRAF p.Gly596Val Pathogenic ★★★ same condition
BRAF p.Leu485Phe Pathogenic ★★★ ⚠ same condition
BRAF p.Phe247Leu 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-ala34val (accessed [today's date]).

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