Is CARD10 p.Ser466= (c.1398C>T) pathogenic?

CARD10 p.Ser466= (c.1398C>T) is classified Benign in CARD10 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-21). Common (popmax 26.8%, eas) — too common for a highly-penetrant pathogenic allele; Associated with CARD10-related disorder.

What condition is associated with CARD10 p.Ser466= (c.1398C>T)?

CARD10 p.Ser466= (c.1398C>T) is associated with CARD10-related disorder (ClinVar).

CARD10 p.Ser466=

Q: How common is CARD10 p.Ser466= (c.1398C>T) in the general population?

CARD10 p.Ser466= (c.1398C>T) is common (popmax 26.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1398C>T · rs3817805 · VCV3056227

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 26.8%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

CARD10-related disorder

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 3.8	GERP 0.3, phastCons 1
Overall
CADD	12.54	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 26.8% East Asian · 11,118/41,498 alleles

Filtering AF 26.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 26.2%

Overall 10.8% 167,118/1,553,088 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	26.8%	4
Middle Eastern	19%	5
South Asian	15%	7
Ashkenazi Jewishnot grpmax-eligible	13.9%	7
Admixed American	12.7%	8
Remaining individualsnot grpmax-eligible	11.7%	9
Amishnot grpmax-eligible	10.5%	10
Finnishnot grpmax-eligible	10.2%	10
European (non-Finnish)	10.2%	10
African / African-American	2.44%	41

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: CARD10
Protein: p.Ser466=
Coding: c.1398C>T
MANE Select: NM_014550
dbSNP: rs3817805
Type: single nucleotide variant
Location: chr22:37504755 (GRCh38)
Gene constraint: LOEUF 0.678 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.22

Full CARD10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CARD10-related disorder

Similar variants

CARD10 p.Ala1032Asp Uncertain significance ⚠ same condition
CARD10 p.Glu1019Gln Uncertain significance ⚠ same condition
CARD10 c.1383+7G>A Likely benign same condition
CARD10 c.2477-7G>C Likely benign same condition
CARD10 c.910-6C>T Benign same condition
CARD10 p.Ala528= Benign same condition
CARD10 p.Ala7= Likely benign same condition
CARD10 p.Ala704= Likely benign 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/card10-p-ser466 (accessed [today's date]).

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