Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 13 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0992%, nfe)
Conditions
3
Inborn genetic diseases
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 0.11 | GERP -0.52, phastCons 0.94 |
| Overall | ||
| CADD | 7.729 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0992%
European (non-Finnish) · 1,171/1,180,062 alleles
Filtering AF
0.0945%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0926%
Overall
0.0752%
1,213/1,614,088 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0992% | 1,008 |
| Remaining individualsnot grpmax-eligible | 0.032% | 3,124 |
| Finnishnot grpmax-eligible | 0.0172% | 5,821 |
| Admixed American | 0.00833% | 12,000 |
| African / African-American | 0.00801% | 12,487 |
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
- CLN3
- Protein
- p.Val277=
- Coding
- c.831G>A
- MANE Select
- NM_001042432
- dbSNP
- rs1142183
- Type
- single nucleotide variant
- Location
- chr16:28482632 (GRCh38)
- Gene constraint
- LOEUF 1.022 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 81.81
Similar variants
- CLN3 c.1056+1G>A Likely pathogenic ★★ same condition
- CLN3 c.1056+1G>T Likely pathogenic ★★ same condition
- CLN3 c.1056+3A>C Pathogenic/Likely pathogenic ★★ same condition
- CLN3 c.1197+1G>A Pathogenic/Likely pathogenic ★★ same condition
- CLN3 c.1198-1G>T Pathogenic/Likely pathogenic ★★ same condition
- CLN3 c.125+1G>C Pathogenic ★★ same condition
- CLN3 c.222+1G>A Likely pathogenic ★★ same condition
- CLN3 c.46+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/cln3-p-val277 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown