Is CARD14 p.Ser1002Arg (c.3006C>A) pathogenic?

CARD14 p.Ser1002Arg (c.3006C>A) is classified Uncertain significance in CARD14 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-21). AlphaMissense: likely benign (0.1789); Ultra-rare (popmax 0.0207%, amr); Associated with pityriasis rubra pilaris.

What condition is associated with CARD14 p.Ser1002Arg (c.3006C>A)?

CARD14 p.Ser1002Arg (c.3006C>A) is associated with pityriasis rubra pilaris, psoriasis 2 (ClinVar).

How common is CARD14 p.Ser1002Arg (c.3006C>A) in the general population?

CARD14 p.Ser1002Arg (c.3006C>A) is ultra-rare (popmax 0.0207%, amr) (gnomAD).

What do computational predictors say about CARD14 p.Ser1002Arg (c.3006C>A)?

AlphaMissense predicts likely benign (score 0.1789) — an in-silico prediction, not a clinical call.

CARD14 p.Ser1002Arg

c.3006C>A · rs984646773 · VCV1039431

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1789 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0207%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

pityriasis rubra pilaris

Computational evidence

Protein change
AlphaMissense	0.1789	likely benign
REVEL	0.008	strongly benign-leaning
SaProt	LLR -5.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.7	GERP -2.1
Regional constraint	o/e 0.97	unconstrained · MANE · 27 kb · p 0.27 · regional, not allelic
Overall
CADD	0.288	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0207% Admixed American · 12/58,078 alleles

Filtering AF 0.0119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00926%

Overall 0.00132% 21/1,595,492 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0207%	4,840
Remaining individualsnot grpmax-eligible	0.00162%	61,768
European (non-Finnish)	0.000683%	146,331

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.Ser1002Arg
Coding: c.3006C>A
MANE Select: NM_001366385
dbSNP: rs984646773
Type: single nucleotide variant
Location: chr17:80208336 (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 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-ser1002arg (accessed [today's date]).

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