SIX3 p.Phe14=
c.42C>T · rs772181424 · VCV772996
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0138%, nfe)
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 5.6 | GERP 0.96, phastCons 1 |
| Overall | ||
| CADD | 13.83 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0138%
European (non-Finnish) · 163/1,179,422 alleles
Filtering AF
0.0121%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0114%
Overall
0.0108%
173/1,598,266 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0138% | 7,236 |
| Remaining individualsnot grpmax-eligible | 0.00963% | 10,380 |
| Finnishnot grpmax-eligible | 0.00805% | 12,425 |
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
- SIX3
- Protein
- p.Phe14=
- Coding
- c.42C>T
- MANE Select
- NM_005413
- dbSNP
- rs772181424
- Type
- single nucleotide variant
- Location
- chr2:44942146 (GRCh38)
- Gene constraint
- LOEUF 0.387 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 70.38
Similar variants
- SIX3 p.Phe14Cys Uncertain significance ★★ ⚠ same residue
- SIX3 p.Ala72Val Uncertain significance ★★ ⚠ same type
- SIX3 p.Arg146Cys Uncertain significance ★★ ⚠ same type
- SIX3 p.Arg201His Uncertain significance ★★ ⚠ same type
- SIX3 p.Arg281Ser Uncertain significance ★★ same type
- SIX3 p.Asp205His Uncertain significance ★★ ⚠ same type
- SIX3 p.Gly103Arg Uncertain significance ★★ ⚠ same type
- SIX3 p.Gly244Cys 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/six3-p-phe14 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown