Is CARD14 p.Pro827= (c.2481C>T) pathogenic?

CARD14 p.Pro827= (c.2481C>T) is classified Benign/Likely benign in CARD14 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 15.1%, sas) — too common for a highly-penetrant pathogenic allele; Associated with psoriasis 2.

What condition is associated with CARD14 p.Pro827= (c.2481C>T)?

CARD14 p.Pro827= (c.2481C>T) is associated with psoriasis 2, pityriasis rubra pilaris (ClinVar).

CARD14 p.Pro827=

Q: How common is CARD14 p.Pro827= (c.2481C>T) in the general population?

CARD14 p.Pro827= (c.2481C>T) is common (popmax 15.1%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2481C>T · rs61757652 · VCV1167400

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 15.1%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

psoriasis 2

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 0.003	GERP -2.5, phastCons 0.85
Overall
CADD	3.324	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 15.1% South Asian · 13,743/91,060 alleles

Filtering AF 14.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 14.8%

Overall 8.02% 129,464/1,613,570 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	15.1%	7
Admixed American	11.5%	9
Ashkenazi Jewishnot grpmax-eligible	10.7%	9
East Asian	9.36%	11
Remaining individualsnot grpmax-eligible	8.65%	12
Middle Eastern	8.07%	12
Finnishnot grpmax-eligible	7.66%	13
European (non-Finnish)	7.4%	14
African / African-American	4.48%	22
Amishnot grpmax-eligible	4.17%	24

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.Pro827=
Coding: c.2481C>T
MANE Select: NM_001366385
dbSNP: rs61757652
Type: single nucleotide variant
Location: chr17:80205117 (GRCh38)
Gene constraint: LOEUF 1.222 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 75.89
Residue 827: the guanylate kinase-like domain

Full CARD14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

psoriasis 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pityriasis rubra pilaris

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-pro827 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown