Is CASP9 p.Gln44Glu (c.130C>G) pathogenic?

CASP9 p.Gln44Glu (c.130C>G) is classified Benign in CASP9 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-12). AlphaMissense: likely benign (0.1349); Very rare (popmax 0.0049%, nfe); Associated with CASP9-related disorder.

What condition is associated with CASP9 p.Gln44Glu (c.130C>G)?

CASP9 p.Gln44Glu (c.130C>G) is associated with CASP9-related disorder (ClinVar).

How common is CASP9 p.Gln44Glu (c.130C>G) in the general population?

CASP9 p.Gln44Glu (c.130C>G) is very rare (popmax 0.0049%, nfe) (gnomAD).

What do computational predictors say about CASP9 p.Gln44Glu (c.130C>G)?

AlphaMissense predicts likely benign (score 0.1349) — an in-silico prediction, not a clinical call.

CASP9 p.Gln44Glu

c.130C>G · rs201250353 · VCV3050328

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1349 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0049%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CASP9-related disorder

Computational evidence

Protein change
AlphaMissense	0.1349	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -8.30	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 0.15, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 31 kb · p 0.1 · regional, not allelic
Overall
CADD	23.2	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 0.0049% European (non-Finnish) · 55/1,121,384 alleles

Filtering AF 0.00386% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00346%

Overall 0.0186% 275/1,480,810 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.654%	153
Remaining individualsnot grpmax-eligible	0.0674%	1,484
European (non-Finnish)grpmax	0.0049%	20,389
Admixed American	0.00445%	22,468
African / African-American	0.00164%	60,846

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CASP9
Protein: p.Gln44Glu
Coding: c.130C>G
MANE Select: NM_001229
dbSNP: rs201250353
Type: single nucleotide variant
Location: chr1:15524071 (GRCh38)
Gene constraint: LOEUF 0.994 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.86 · 13 PDB
Residue 44: an α-helix; the card domain

Full CASP9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CASP9-related disorder

Similar variants

CASP9 c.453+8T>C Benign same condition
CASP9 c.721-5T>C Benign same condition
CASP9 p.Ala220= Likely benign same condition
CASP9 p.Gln221Arg Benign same condition
CASP9 p.Leu384= Likely benign same condition
CASP9 p.Leu8= Benign same condition
CASP9 p.Met157Val Likely benign same condition
CASP9 p.Phe136= Benign 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/casp9-p-gln44glu (accessed [today's date]).

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