SIX2 p.Pro118=
c.354G>C · rs1457601978 · VCV2729397
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000339%, 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 -1.8 | GERP -1.4 |
| Overall | ||
| CADD | 12.81 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000339%
European (non-Finnish) · 4/1,179,970 alleles
Filtering AF
7.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.4e-05%
Overall
0.000248%
4/1,613,848 alleles · very rare
exomes 3/1,461,606 · genomes 1/152,242 · joint denominator
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
- SIX2
- Protein
- p.Pro118=
- Coding
- c.354G>C
- MANE Select
- NM_016932
- dbSNP
- rs1457601978
- Type
- single nucleotide variant
- Location
- chr2:45008757 (GRCh38)
- Gene constraint
- LOEUF 1.24 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.99
Similar variants
- SIX2 p.Pro118Gln Uncertain significance ★ ⚠ same residue
- SIX2 p.Pro118Leu Uncertain significance ★ ⚠ same residue
- SIX2 p.Asn280Ser Uncertain significance ★★ ⚠ same type
- SIX2 p.Gly220Val Uncertain significance ★★ ⚠ same type
- SIX2 p.Gly261Ser Uncertain significance ★★ ⚠ same type
- SIX2 p.Pro235Leu Uncertain significance ★★ ⚠ same type
- SIX2 p.Pro236Leu Uncertain significance ★★ ⚠ same type
- SIX2 p.Pro250Leu 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/six2-p-pro118 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown