Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 10 submitters
gnomAD v4.1
Common
common (popmax 43.4%, sas) — too common for a highly-penetrant pathogenic allele
Conditions
2
pityriasis rubra pilaris
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 4.5 | GERP -0.057, phastCons 1 |
| Overall | ||
| CADD | 9.425 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
43.4%
South Asian · 36,308/83,632 alleles
Filtering AF
43%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 42.9%
Overall
37.6%
584,178/1,554,468 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 43.4% | 2 |
| Middle Eastern | 41.8% | 2 |
| African / African-American | 41.6% | 2 |
| Finnishnot grpmax-eligible | 38.5% | 3 |
| European (non-Finnish) | 37.9% | 3 |
| Remaining individualsnot grpmax-eligible | 37.4% | 3 |
| Ashkenazi Jewishnot grpmax-eligible | 36.8% | 3 |
| Amishnot grpmax-eligible | 33.1% | 3 |
| Admixed American | 27.5% | 4 |
| East Asian | 23.1% | 4 |
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
- CARD14
- Protein
- p.Glu211=
- Coding
- c.633G>A
- MANE Select
- NM_001366385
- dbSNP
- rs4889990
- Type
- single nucleotide variant
- Location
- chr17:80184196 (GRCh38)
- Gene constraint
- LOEUF 1.222 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.89
Similar variants
- CARD14 c.349+1G>A Pathogenic ★★ same condition
- CARD14 p.Leu156Pro Pathogenic/Likely pathogenic ★★ same condition
- CARD14 p.Met119Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
- CARD14 c.1089+5C>G Uncertain significance ★★ same condition
- CARD14 c.1357-1G>A Uncertain significance ★★ same condition
- CARD14 c.2569+2T>A Uncertain significance ★★ same condition
- CARD14 c.963+5C>T Uncertain significance ★★ same condition
- CARD14 p.Ala208Val Uncertain significance ★★ ⚠ 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/card14-p-glu211 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown