Is CASP10 p.Ser59= (c.177A>G) pathogenic?

CASP10 p.Ser59= (c.177A>G) is classified Benign/Likely benign in CASP10 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-04). Common (popmax 52.6%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with autoimmune lymphoproliferative syndrome type 2A.

What condition is associated with CASP10 p.Ser59= (c.177A>G)?

CASP10 p.Ser59= (c.177A>G) is associated with autoimmune lymphoproliferative syndrome type 2A (ClinVar).

How is Autoimmune lymphoproliferative syndrome inherited?

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

CASP10 p.Ser59=

Q: How common is CASP10 p.Ser59= (c.177A>G) in the general population?

CASP10 p.Ser59= (c.177A>G) is common (popmax 52.6%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.177A>G · rs3900115 · VCV333418

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Common

common (popmax 52.6%, nfe) — too common for a highly-penetrant pathogenic allele

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 -2.9	GERP -3.4
Overall
CADD	0.777	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 52.6% European (non-Finnish) · 620,672/1,179,754 alleles

Filtering AF 52.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 52.5%

Overall 49.6% 801,132/1,613,588 alleles · common

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	52.6%	2
Ashkenazi Jewishnot grpmax-eligible	52.3%	2
Finnishnot grpmax-eligible	50.1%	2
African / African-American	48.5%	2
Remaining individualsnot grpmax-eligible	48.2%	2
Amishnot grpmax-eligible	42%	2
Middle Eastern	40.9%	2
Admixed American	37.5%	3
South Asian	35.3%	3
East Asian	20%	5

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.Ser59=
Coding: c.177A>G
MANE Select: NM_032977
dbSNP: rs3900115
Type: single nucleotide variant
Location: chr2:201185954 (GRCh38)
Gene constraint: LOEUF 1.046 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 69.54
Residue 59: the ded 1 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.Ser59Trp 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
CASP10 p.Ala248Val 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-ser59 (accessed [today's date]).

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