CLN6 p.Thr40=
c.120G>A · rs1034192926 · VCV1400609
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00534%, afr)
Conditions
2
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.265 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -3 |
| Overall | ||
| CADD | 0.123 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00534%
African / African-American · 4/74,888 alleles
Filtering AF
0.00175%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.00167%
27/1,613,792 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00534% | 18,722 |
| South Asian | 0.0022% | 45,537 |
| Admixed American | 0.00167% | 59,988 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,470 |
| Finnishnot grpmax-eligible | 0.00156% | 63,942 |
| European (non-Finnish) | 0.00153% | 65,552 |
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
- CLN6
- Protein
- p.Thr40=
- Coding
- c.120G>A
- MANE Select
- NM_017882
- dbSNP
- rs1034192926
- Type
- single nucleotide variant
- Location
- chr15:68218614 (GRCh38)
- Gene constraint
- LOEUF 1.015 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.86
Similar variants
- CLN6 p.Thr40Met Uncertain significance ★★ ⚠ same residue
- CLN6 p.Thr40Lys Uncertain significance ★ ⚠ same residue
- CLN6 c.297+1G>A Pathogenic/Likely pathogenic ★★ same condition
- CLN6 c.486+1G>A Likely pathogenic ★★ same condition
- CLN6 c.543-1G>A Likely pathogenic ★★ same condition
- CLN6 c.665+1G>A Pathogenic/Likely pathogenic ★★ same condition
- CLN6 c.84-1G>A Pathogenic/Likely pathogenic ★★ same condition
- CLN6 p.Arg103Gln Pathogenic/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/cln6-p-thr40 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown