Is CARD8 p.Ser339= (c.1017C>T) pathogenic?

CARD8 p.Ser339= (c.1017C>T) is classified Likely benign in CARD8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). Ultra-rare (popmax 0.0156%, eas).

How common is CARD8 p.Ser339= (c.1017C>T) in the general population?

CARD8 p.Ser339= (c.1017C>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

CARD8 p.Ser339=

c.1017C>T · rs760059064 · VCV744277

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

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 -3.6	GERP -2.8
Overall
CADD	1.699	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,780 alleles

Filtering AF 0.00727% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.00187% 30/1,608,088 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,397
Remaining individualsnot grpmax-eligible	0.0113%	8,886
Admixed American	0.00841%	11,887
Finnishnot grpmax-eligible	0.00156%	63,922
African / African-American	0.00134%	74,672
European (non-Finnish)	0.000765%	130,698

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.Ser339=
Coding: c.1017C>T
MANE Select: NM_001184900
dbSNP: rs760059064
Type: single nucleotide variant
Location: chr19:48230456 (GRCh38)
Gene constraint: LOEUF 0.883 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.42 · 5 PDB
Residue 339: a UniProt-annotated variant site (in ibd30); the fiind domain; the 'upa' region; a β-strand

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

Similar variants

CARD8 p.Ser339Arg Uncertain significance ★ same residue
CARD8 p.Ser339Gly Likely benign ★ 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
CARD8 p.Arg103His Uncertain significance ★★ same type
CARD8 p.Arg20Trp Uncertain significance ★★ same type
CARD8 p.Arg304Gln 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-ser339 (accessed [today's date]).

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