DEF6 p.Cys267=
c.801C>T · rs981772543 · VCV1541922
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00429%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.42 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -9.6 | GERP -3.7 |
| Overall | ||
| CADD | 1.82 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00429%
African / African-American · 3/69,974 alleles
Filtering AF
0.00114%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000616%
Overall
0.000658%
10/1,520,902 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00429% | 23,325 |
| Admixed American | 0.00357% | 27,978 |
| Remaining individualsnot grpmax-eligible | 0.00355% | 28,166 |
| South Asian | 0.00224% | 44,658 |
| European (non-Finnish) | 8.88e-05% | 1,125,758 |
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
- DEF6
- Protein
- p.Cys267=
- Coding
- c.801C>T
- MANE Select
- NM_022047
- dbSNP
- rs981772543
- Type
- single nucleotide variant
- Location
- chr6:35312766 (GRCh38)
- Gene constraint
- LOEUF 0.61 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.91
- Residue 267
- the ph domain
Similar variants
- DEF6 p.Ala395Glu Uncertain significance ★★ ⚠ same type
- DEF6 p.Ala617Val Uncertain significance ★★ ⚠ same type
- DEF6 p.Arg104Pro Uncertain significance ★★ ⚠ same type
- DEF6 p.Arg104Trp Uncertain significance ★★ ⚠ same type
- DEF6 p.Arg192Cys Uncertain significance ★★ ⚠ same type
- DEF6 p.Arg195Gln Uncertain significance ★★ ⚠ same type
- DEF6 p.Arg349Leu Uncertain significance ★★ ⚠ same type
- DEF6 p.Arg4Cys Uncertain significance ★★ ⚠ 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/def6-p-cys267 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown