Is CARD8 p.Arg353= (c.1059C>T) pathogenic?

CARD8 p.Arg353= (c.1059C>T) is classified Likely benign in CARD8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-15). Very rare (popmax 0.00134%, afr).

How common is CARD8 p.Arg353= (c.1059C>T) in the general population?

CARD8 p.Arg353= (c.1059C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

CARD8 p.Arg353=

c.1059C>T · rs752071016 · VCV2828947

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

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 -2.1	GERP -3.2
Overall
CADD	0.461	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,784 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000187% 3/1,605,160 alleles · very rare exomes 2/1,452,960 · genomes 1/152,200 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,784
European (non-Finnish)	0.00017%	587,082

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: CARD8
Protein: p.Arg353=
Coding: c.1059C>T
MANE Select: NM_001184900
dbSNP: rs752071016
Type: single nucleotide variant
Location: chr19:48221832 (GRCh38)
Gene constraint: LOEUF 0.883 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.42 · 5 PDB
Residue 353: a UniProt-annotated variant site (in ibd30); the fiind domain; the 'upa' region; an α-helix

Full CARD8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CARD8 p.Arg353Cys Uncertain significance ★★ same residue
CARD8 p.Arg353Gly Uncertain significance ★ same residue
CARD8 p.Arg353His Uncertain significance ★ same residue
CARD8 p.Arg353Leu Uncertain significance ★ same residue
CARD8 p.Arg353Pro Uncertain significance ★ same residue
CARD8 c.1035+5G>A Uncertain significance ★★ same type
CARD8 p.Ala442Pro Uncertain significance ★★ same type
CARD8 p.Ala97Val Uncertain significance ★★ same type

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/card8-p-arg353 (accessed [today's date]).

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