Is BRAF p.Asp22Tyr (c.64G>T) pathogenic?

BRAF p.Asp22Tyr (c.64G>T) is classified Uncertain significance in BRAF (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-14). AlphaMissense: likely pathogenic (0.7186); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with BRAF p.Asp22Tyr (c.64G>T)?

BRAF p.Asp22Tyr (c.64G>T) is associated with Cardiovascular phenotype (ClinVar).

How common is BRAF p.Asp22Tyr (c.64G>T) in the general population?

BRAF p.Asp22Tyr (c.64G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRAF p.Asp22Tyr (c.64G>T)?

AlphaMissense predicts likely pathogenic (score 0.7186) — an in-silico prediction, not a clinical call.

BRAF p.Asp22Tyr

c.64G>T · rs397507456 · VCV1753906

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7186 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.7186	likely pathogenic
REVEL	0.401	indeterminate
SaProt	LLR -7.62	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 5.2	GERP 2.8, phastCons 1
Overall
CADD	29.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BRAF
Protein: p.Asp22Tyr
Coding: c.64G>T
MANE Select: NM_004333
dbSNP: rs397507456
Type: single nucleotide variant
Location: chr7:140924640 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.87 · 135 PDB
Residue 22: the 'disordered' region

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BRAF p.Asp22Asn Benign ★★★ same residue
BRAF p.Asp22Glu Uncertain significance ★★ ⚠ same residue
BRAF p.Asp22Val Uncertain significance ★★ ⚠ same residue
BRAF p.Asn236Lys Likely pathogenic ★★ same condition
BRAF p.Gln262Arg Pathogenic/Likely pathogenic ★★ same condition
BRAF p.Glu501Lys Pathogenic/Likely pathogenic ★★ same condition
BRAF c.2127+4A>G Uncertain significance ★★ same condition
BRAF p.Ala27Gly Uncertain significance ★★ ⚠ 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-asp22tyr (accessed [today's date]).

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