Is CARD14 p.Asp659= (c.1977C>T) pathogenic?

CARD14 p.Asp659= (c.1977C>T) is classified Likely benign in CARD14 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-17). Ultra-rare (popmax 0.0309%, sas); Associated with psoriasis 2.

What condition is associated with CARD14 p.Asp659= (c.1977C>T)?

CARD14 p.Asp659= (c.1977C>T) is associated with psoriasis 2, pityriasis rubra pilaris (ClinVar).

How common is CARD14 p.Asp659= (c.1977C>T) in the general population?

CARD14 p.Asp659= (c.1977C>T) is ultra-rare (popmax 0.0309%, sas) (gnomAD).

CARD14 p.Asp659=

c.1977C>T · rs200737962 · VCV574056

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0309%, sas)

Conditions

psoriasis 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.05	GERP -2.4, phastCons 0.052
Overall
CADD	5.991	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0309% South Asian · 28/90,708 alleles

Filtering AF 0.0218% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0189%

Overall 0.00589% 95/1,611,880 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0309%	3,240
African / African-American	0.0187%	5,357
East Asian	0.00669%	14,958
Remaining individualsnot grpmax-eligible	0.00641%	15,600
European (non-Finnish)	0.00373%	26,792
Admixed American	0.00334%	29,936

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.Asp659=
Coding: c.1977C>T
MANE Select: NM_001366385
dbSNP: rs200737962
Type: single nucleotide variant
Location: chr17:80201869 (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

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-asp659 (accessed [today's date]).

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