FANCD2 p.Leu686=
c.2058G>A · rs773593671 · VCV700286
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0646%, eas)
Conditions
2
Fanconi anemia complementation group D2
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.25 | GERP -3.1, phastCons 0.81 |
| Overall | ||
| CADD | 1.109 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0646%
East Asian · 29/44,892 alleles
Filtering AF
0.0461%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0399%
Overall
0.00211%
34/1,614,136 alleles · ultra-rare
exomes 27/1,461,798 · genomes 7/152,338 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0646% | 1,548 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,502 |
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
- FANCD2
- Protein
- p.Leu686=
- Coding
- c.2058G>A
- MANE Select
- NM_001018115
- dbSNP
- rs773593671
- Type
- single nucleotide variant
- Location
- chr3:10064765 (GRCh38)
- Gene constraint
- LOEUF 0.777 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 77.24 · 13 PDB
Similar variants
- FANCD2 p.Leu686Pro Uncertain significance ★★ ⚠ same residue
- FANCD2 c.1279-1G>A Pathogenic/Likely pathogenic ★★ same condition
- FANCD2 c.1279-2A>G Likely pathogenic ★★ same condition
- FANCD2 c.1948-16T>G Pathogenic ★★ same condition
- FANCD2 c.1948-6C>A Pathogenic/Likely pathogenic ★★ same condition
- FANCD2 c.206-1G>T Likely pathogenic ★★ same condition
- FANCD2 c.2169-1G>C Likely pathogenic ★★ same condition
- FANCD2 c.2269+1G>A Likely 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/fancd2-p-leu686 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown