Is CARD10 p.Arg1005Cys (c.3013C>T) pathogenic?

CARD10 p.Arg1005Cys (c.3013C>T) is classified Uncertain significance in CARD10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-09). AlphaMissense: likely pathogenic (0.7506); Very rare (popmax 0.00186%, amr).

How common is CARD10 p.Arg1005Cys (c.3013C>T) in the general population?

CARD10 p.Arg1005Cys (c.3013C>T) is very rare (popmax 0.00186%, amr) (gnomAD).

What do computational predictors say about CARD10 p.Arg1005Cys (c.3013C>T)?

AlphaMissense predicts likely pathogenic (score 0.7506) — an in-silico prediction, not a clinical call.

CARD10 p.Arg1005Cys

c.3013C>T · VCV3263290

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7506 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00186%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7506	likely pathogenic
REVEL	0.425	indeterminate
SaProt	LLR -9.53	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.44, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 25 kb · p 0.0012 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00186% Admixed American · 1/53,828 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000283% 4/1,414,398 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00186%	53,828
Remaining individualsnot grpmax-eligible	0.00164%	60,962
European (non-Finnish)	0.000172%	580,511

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.Arg1005Cys
Coding: c.3013C>T
MANE Select: NM_014550
Type: single nucleotide variant
Location: chr22:37491245 (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

Similar variants

CARD10 p.Thr436Met Uncertain significance ★★ ⚠ same type
CARD10 p.Ala382Thr Benign ★★ same type
CARD10 p.Glu327= Likely benign ★★ same type
CARD10 p.Ile940= Benign/Likely benign ★★ same type
CARD10 p.Lys514Arg Benign ★★ same type
CARD10 p.Thr383= Benign ★★ same type
CARD10 p.Arg420Cys Likely pathogenic ★ ⚠ same type
CARD10 c.2864+2T>G 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/card10-p-arg1005cys (accessed [today's date]).

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