Is BRAF p.Pro44Leu (c.131C>T) pathogenic?

BRAF p.Pro44Leu (c.131C>T) is classified Uncertain significance in BRAF (ClinVar, Single submitter, 1 submitter; last evaluated 2015-06-01). AlphaMissense: ambiguous (0.3902); No allele count reported in gnomAD v4.1 (AN 1,531,782).

How common is BRAF p.Pro44Leu (c.131C>T) in the general population?

BRAF p.Pro44Leu (c.131C>T) is no allele count reported in gnomAD v4.1 (AN 1,531,782) (gnomAD).

What do computational predictors say about BRAF p.Pro44Leu (c.131C>T)?

AlphaMissense predicts ambiguous (score 0.3902) — an in-silico prediction, not a clinical call.

BRAF p.Pro44Leu

c.131C>T · rs794726917 · VCV193280

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3902 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,531,782)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3902	ambiguous
REVEL	0.288	benign-leaning
SaProt	LLR -7.10	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 2.6, phastCons 1
Overall
CADD	24.8	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

No allele count reported in gnomAD v4.1 (AN 1,531,782). 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.Pro44Leu
Coding: c.131C>T
MANE Select: NM_004333
dbSNP: rs794726917
Type: single nucleotide variant
Location: chr7:140924573 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.87 · 135 PDB
Residue 44: an α-helix

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

Similar variants

BRAF p.Pro44Thr Uncertain significance ★ ⚠ same residue
BRAF p.Pro44= Likely benign ★ 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
BRAF p.Gly265Arg Likely 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-pro44leu (accessed [today's date]).

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