Is BRAF p.Pro25Thr (c.73C>A) pathogenic?

BRAF p.Pro25Thr (c.73C>A) is classified Uncertain significance in BRAF (ClinVar, Single submitter, 1 submitter; last evaluated 2014-08-05). AlphaMissense: likely benign (0.0851); Absent from gnomAD v4.1.

How common is BRAF p.Pro25Thr (c.73C>A) in the general population?

BRAF p.Pro25Thr (c.73C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRAF p.Pro25Thr (c.73C>A)?

AlphaMissense predicts likely benign (score 0.0851) — an in-silico prediction, not a clinical call.

BRAF p.Pro25Thr

c.73C>A · rs730880412 · VCV180791

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0851 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,513,418)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0851	likely benign
REVEL	0.179	moderately benign-leaning
SaProt	LLR -7.48	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 4.1	GERP 1.1, phastCons 1
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,513,418). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BRAF
Protein: p.Pro25Thr
Coding: c.73C>A
MANE Select: NM_004333
dbSNP: rs730880412
Type: single nucleotide variant
Location: chr7:140924631 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.87 · 135 PDB
Residue 25: the 'disordered' region

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

Similar variants

BRAF p.Pro25Ser Uncertain significance ★★ ⚠ same residue
BRAF p.Pro25= Likely benign ★★ same residue
BRAF p.Pro25Leu Uncertain significance ★ ⚠ same residue
BRAF p.Ala246Pro Pathogenic ★★★ same type
BRAF p.Asn581Asp Pathogenic ★★★ same type
BRAF p.Asp594Val Pathogenic ★★★ same type
BRAF p.Cys532Tyr Likely pathogenic ★★★ same type
BRAF p.Gln257Arg 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-pro25thr (accessed [today's date]).

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