CARD14 p.Asp991=
c.2973C>T · rs554956821 · VCV1583461
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
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 -8.4 | GERP -1.9 |
| Overall | ||
| CADD | 0.463 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,044 alleles
Filtering AF
0.00224%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00199%
Overall
0.00287%
46/1,605,488 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,044 |
| African / African-American | 0.004% | 25,005 |
| South Asian | 0.00336% | 29,780 |
| Remaining individualsnot grpmax-eligible | 0.00322% | 31,097 |
| European (non-Finnish) | 0.00306% | 32,699 |
| Admixed American | 0.0017% | 58,770 |
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.Asp991=
- Coding
- c.2973C>T
- MANE Select
- NM_001366385
- dbSNP
- rs554956821
- Type
- single nucleotide variant
- Location
- chr17:80208303 (GRCh38)
- Gene constraint
- LOEUF 1.222 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.89
Similar variants
- CARD14 p.Asp991Glu Uncertain significance ★ ⚠ same residue
- CARD14 p.Asp991Gly Uncertain significance ★ ⚠ same residue
- 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
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-asp991 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown