Is CASP10 p.Leu83Pro (c.248T>C) pathogenic?

CASP10 p.Leu83Pro (c.248T>C) is classified Uncertain significance in CASP10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-04). AlphaMissense: likely pathogenic (0.9159); Absent from gnomAD v4.1; Associated with autoimmune lymphoproliferative syndrome type 2A.

What condition is associated with CASP10 p.Leu83Pro (c.248T>C)?

CASP10 p.Leu83Pro (c.248T>C) is associated with autoimmune lymphoproliferative syndrome type 2A (ClinVar).

How common is CASP10 p.Leu83Pro (c.248T>C) in the general population?

CASP10 p.Leu83Pro (c.248T>C) is absent from gnomAD v4.1 (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.Leu83Pro (c.248T>C)?

AlphaMissense predicts likely pathogenic (score 0.9159) — an in-silico prediction, not a clinical call.

CASP10 p.Leu83Pro

c.248T>C · rs2469360695 · VCV2926874

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9159 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autoimmune lymphoproliferative syndrome type 2A

Computational evidence

Protein change
AlphaMissense	0.9159	likely pathogenic · top 6% in CASP10
REVEL	0.845	moderately pathogenic-leaning
SaProt	LLR -15.95	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 1.7, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 32 kb · p 0.98 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CASP10
Protein: p.Leu83Pro
Coding: c.248T>C
MANE Select: NM_032977
dbSNP: rs2469360695
Type: single nucleotide variant
Location: chr2:201186025 (GRCh38)
Gene constraint: LOEUF 1.046 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 69.54
Residue 83: 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.Leu83Phe Uncertain significance ★★ ⚠ same residue
CASP10 p.Leu83Val Uncertain significance ★★ ⚠ same residue
CASP10 p.Leu83= Likely benign ★ same residue
CASP10 p.Leu83del 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

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-leu83pro (accessed [today's date]).

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