Is CARD14 p.Arg720= (c.2160C>T) pathogenic?

CARD14 p.Arg720= (c.2160C>T) is classified Likely benign in CARD14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-10). Ultra-rare (popmax 0.0156%, eas); Associated with pityriasis rubra pilaris.

What condition is associated with CARD14 p.Arg720= (c.2160C>T)?

CARD14 p.Arg720= (c.2160C>T) is associated with pityriasis rubra pilaris, psoriasis 2 (ClinVar).

How common is CARD14 p.Arg720= (c.2160C>T) in the general population?

CARD14 p.Arg720= (c.2160C>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

CARD14 p.Arg720=

c.2160C>T · rs776598351 · VCV1557036

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Conditions

pityriasis rubra pilaris

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.015	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.2	GERP -2.9
Overall
CADD	1.123	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,860 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.0018% 29/1,613,318 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,409
South Asian	0.0022%	45,545
Admixed American	0.00167%	60,000
Remaining individualsnot grpmax-eligible	0.0016%	62,480
European (non-Finnish)	0.00144%	69,414
African / African-American	0.00133%	74,916

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.Arg720=
Coding: c.2160C>T
MANE Select: NM_001366385
dbSNP: rs776598351
Type: single nucleotide variant
Location: chr17:80202361 (GRCh38)
Gene constraint: LOEUF 1.222 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 75.89

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

Disease context

pityriasis rubra pilaris — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: psoriasis 2

Similar variants

CARD14 p.Arg720Cys Uncertain significance ★ ⚠ same residue
CARD14 p.Arg720His Conflicting classifications of pathogenicity ★ ⚠ 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-arg720 (accessed [today's date]).

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