Is CASP10 p.Ser141= (c.423G>A) pathogenic?

CASP10 p.Ser141= (c.423G>A) is classified Likely benign in CASP10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-11). Ultra-rare (popmax 0.0312%, eas); Associated with autoimmune lymphoproliferative syndrome type 2A.

What condition is associated with CASP10 p.Ser141= (c.423G>A)?

CASP10 p.Ser141= (c.423G>A) is associated with autoimmune lymphoproliferative syndrome type 2A (ClinVar).

How common is CASP10 p.Ser141= (c.423G>A) in the general population?

CASP10 p.Ser141= (c.423G>A) is ultra-rare (popmax 0.0312%, eas) (gnomAD).

How is Autoimmune lymphoproliferative syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CASP10 p.Ser141=

c.423G>A · rs768931544 · VCV1113561

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0312%, eas)

Conditions

autoimmune lymphoproliferative syndrome type 2A

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	GERP -3
Overall
CADD	0.94	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0312% East Asian · 14/44,882 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.0018% 29/1,613,636 alleles · ultra-rare exomes 27/1,461,474 · genomes 2/152,162 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0312%	3,206
South Asian	0.00549%	18,218
African / African-American	0.00267%	37,453
Admixed American	0.00167%	59,974
Remaining individualsnot grpmax-eligible	0.0016%	62,474
European (non-Finnish)	0.000509%	196,619

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: CASP10
Protein: p.Ser141=
Coding: c.423G>A
MANE Select: NM_032977
dbSNP: rs768931544
Type: single nucleotide variant
Location: chr2:201187781 (GRCh38)
Gene constraint: LOEUF 1.046 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 69.54
Residue 141: the ded 2 domain

Full CASP10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autoimmune lymphoproliferative syndrome type 2A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autoimmune lymphoproliferative syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: All ages

Similar variants

CASP10 p.Ser141Leu Uncertain significance ★★ ⚠ same residue
CASP10 p.Ser141Ter Uncertain significance ★★ same residue
CASP10 c.1415+2T>C Uncertain significance ★★ same condition
CASP10 c.1416-3C>A Uncertain significance ★★ same condition
CASP10 c.347+2T>G Uncertain significance ★★ same condition
CASP10 c.684+1G>A Uncertain significance ★★ same condition
CASP10 c.922+5G>A Uncertain significance ★★ same condition
CASP10 p.Ala237Glu 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/casp10-p-ser141 (accessed [today's date]).

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