BRCA2 p.Phe2562Val
c.7684T>G · rs80358995 · VCV182243
Computational evidence
| Protein change | ||
| AlphaMissense | 0.6993 | likely pathogenic · top 5% in BRCA2 |
|---|---|---|
| REVEL | 0.918 | moderately pathogenic-leaning |
| ⇒ AlphaMissense and REVEL both call this damaging. | ||
| Splicing | ||
| SpliceAI | Δ0.27 | acceptor gain at this position · raw score · deltas |
| Constraint at this position | ||
| Conservation | phyloP 7.8 | GERP 2, phastCons 1 |
| Regional constraint | o/e 1.03 | unconstrained · MANE · 47 kb · p 0.059 · regional, not allelic |
| Overall | ||
| CADD | 29.1 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 + genomesAbsent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
ClinGen expert panel — ENIGMA BRCA1 and BRCA2 VCEP
Uncertain Significance for BRCA2-related cancer predisposition. Applied ACMG criteria (verbatim):
PM2_Supporting PP3
Curation rationale (ClinGen, verbatim)
The c.7684T>G variant in BRCA2 is a missense variant predicted to cause substitution of Phenylalanine by Valine at amino acid 2562 (p.(Phe2562Val)). This variant is absent from gnomAD v2.1 (exomes only, non-cancer subset, read depth ≥25) and gnomAD v3.1 (non-cancer subset, read depth ≥25) (PM2_Supporting met). This BRCA2 missense variant has a SpliceAI score of 0.27, predicting an impact on splicing (score threshold >0.20) (PP3 met). Missense variant predicted to alter splicing, functional data considered only from assays that measure effect via mRNA and protein. Results from two calibrated studies with cDNA based design not considered for code application (PMID:38417439, 32444794). Reported by two calibrated studies with discordant results. Functional effect similar to pathogenic control variants (PMID:39779857) and similar to benign control variants (PMID:39779848) (PS3 and BS3 not met). In summary, this variant meets the criteria to be classified as a Variant of uncertain significance for BRCA2-related cancer predisposition based on the ACMG/AMP criteria applied as specified by the ENIGMA BRCA1/2 VCEP (PM2_Supporting, PP3).
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Variant & gene context
- Gene
- BRCA2
- Protein
- p.Phe2562Val
- Coding
- c.7684T>G
- MANE Select
- NM_000059
- dbSNP
- rs80358995
- Type
- single nucleotide variant
- Location
- chr13:32357808 (GRCh38)
- Gene constraint
- LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Residue 2562
- the 'interaction with sem1' region
Similar variants
- BRCA2 p.Phe2562Cys Likely pathogenic ★★★ same residue
- BRCA2 p.Phe2562Ile Uncertain significance ★★ ⚠ same residue
- BRCA2 p.Phe2562Leu Uncertain significance ★ ⚠ same residue
- BRCA2 c.316+2T>C Pathogenic ★★★ same condition
- BRCA2 c.316+5G>A Pathogenic ★★★ same condition
- BRCA2 c.316+5G>C Pathogenic ★★★ same condition
- BRCA2 c.475+1G>A Pathogenic ★★★ same condition
- BRCA2 c.475+1G>T 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/brca2-p-phe2562val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown