Is CASP10 p.Ala519= (c.1557A>G) pathogenic?

CASP10 p.Ala519= (c.1557A>G) is classified Likely benign in CASP10 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-25). Ultra-rare (popmax 0.02%, eas); Associated with autoimmune lymphoproliferative syndrome type 2A.

What condition is associated with CASP10 p.Ala519= (c.1557A>G)?

CASP10 p.Ala519= (c.1557A>G) is associated with autoimmune lymphoproliferative syndrome type 2A (ClinVar).

How common is CASP10 p.Ala519= (c.1557A>G) in the general population?

CASP10 p.Ala519= (c.1557A>G) is ultra-rare (popmax 0.02%, 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.Ala519=

c.1557A>G · rs747642517 · VCV2927776

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, 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 -2.5	GERP -3.1
Overall
CADD	0.205	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% East Asian · 9/44,890 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.000991% 16/1,613,888 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.02%	4,988
Remaining individualsnot grpmax-eligible	0.0032%	31,239
Admixed American	0.00167%	59,994
European (non-Finnish)	0.000339%	294,989

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.Ala519=
Coding: c.1557A>G
MANE Select: NM_032977
dbSNP: rs747642517
Type: single nucleotide variant
Location: chr2:201217729 (GRCh38)
Gene constraint: LOEUF 1.046 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 69.54

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.Ala519Glu Uncertain significance ★ same residue
CASP10 p.Ser519= Likely benign ★ 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-ala519 (accessed [today's date]).

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