Is CASP2 p.Arg44Ter (c.130C>T) pathogenic?

CASP2 p.Arg44Ter (c.130C>T) is classified Pathogenic in CASP2 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-04-09). Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with CASP2 p.Arg44Ter (c.130C>T)?

CASP2 p.Arg44Ter (c.130C>T) is associated with Inborn genetic diseases, intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly (ClinVar).

How common is CASP2 p.Arg44Ter (c.130C>T) in the general population?

CASP2 p.Arg44Ter (c.130C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

CASP2 p.Arg44Ter

c.130C>T · rs910498292 · VCV2499471

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 11
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 3.3, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,074 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000434% 7/1,613,796 alleles · very rare exomes 7/1,461,712 · genomes 0/152,084 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,074
European (non-Finnish)	0.000509%	196,643

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: CASP2
Protein: p.Arg44Ter
Coding: c.130C>T
MANE Select: NM_032982
dbSNP: rs910498292
Type: single nucleotide variant
Location: chr7:143291595 (GRCh38)
Gene constraint: LOEUF 0.936 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.95 · 17 PDB
Residue 44: a UniProt-annotated variant site (in mrt80; likely pathogenic); the card domain

Full CASP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly

Similar variants

CASP2 c.876+1G>T Pathogenic ★ same condition
CASP2 p.Gln392Ter Pathogenic ★ same condition
CASP2 p.His187fs Likely pathogenic ★ same condition
CASP2 p.Tyr386fs Pathogenic ★ same condition
CASP2 p.Gln331Glu Uncertain significance ★★ ⚠ same type
CASP2 p.Ala412= Likely benign ★★ same type
CASP2 p.Gly7= Likely benign ★★ same type
CASP2 p.Ile387= Benign/Likely benign ★★ same type

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/casp2-p-arg44ter (accessed [today's date]).

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