Is CASP10 p.Ser55Pro (c.163T>C) pathogenic?

CASP10 p.Ser55Pro (c.163T>C) is classified Uncertain significance in CASP10 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-27). AlphaMissense: ambiguous (0.5101); Very rare (popmax 0.00203%, nfe); Associated with autoimmune lymphoproliferative syndrome type 2A.

What condition is associated with CASP10 p.Ser55Pro (c.163T>C)?

CASP10 p.Ser55Pro (c.163T>C) is associated with autoimmune lymphoproliferative syndrome type 2A (ClinVar).

How common is CASP10 p.Ser55Pro (c.163T>C) in the general population?

CASP10 p.Ser55Pro (c.163T>C) is very rare (popmax 0.00203%, nfe) (gnomAD).

How is Autoimmune lymphoproliferative syndrome inherited?

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

What do computational predictors say about CASP10 p.Ser55Pro (c.163T>C)?

AlphaMissense predicts ambiguous (score 0.5101) — an in-silico prediction, not a clinical call.

CASP10 p.Ser55Pro

c.163T>C · rs773417904 · VCV1353823

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5101 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00203%, nfe)

Conditions

autoimmune lymphoproliferative syndrome type 2A

Computational evidence

Protein change
AlphaMissense	0.5101	ambiguous
REVEL	0.358	indeterminate
SaProt	LLR -12.59	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4	GERP -3.4
Regional constraint	o/e 1.00	unconstrained · MANE · 32 kb · p 0.98 · regional, not allelic
Overall
CADD	12.68	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 0.00203% European (non-Finnish) · 24/1,180,010 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00149% 24/1,614,032 alleles · very rare

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.Ser55Pro
Coding: c.163T>C
MANE Select: NM_032977
dbSNP: rs773417904
Type: single nucleotide variant
Location: chr2:201185940 (GRCh38)
Gene constraint: LOEUF 1.046 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 69.54
Residue 55: 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 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
CASP10 p.Ala259Thr 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-ser55pro (accessed [today's date]).

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