Is CASP9 p.Ser31= (c.93C>T) pathogenic?

CASP9 p.Ser31= (c.93C>T) is classified Benign in CASP9 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-08). Common (popmax 42.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with CASP9-related disorder.

What condition is associated with CASP9 p.Ser31= (c.93C>T)?

CASP9 p.Ser31= (c.93C>T) is associated with CASP9-related disorder (ClinVar).

CASP9 p.Ser31=

Q: How common is CASP9 p.Ser31= (c.93C>T) in the general population?

CASP9 p.Ser31= (c.93C>T) is common (popmax 42.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.93C>T · rs4645983 · VCV3059411

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 42.6%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

CASP9-related disorder

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 1.1	GERP -2, phastCons 0.29
Overall
CADD	8.356	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 42.6% African / African-American · 30,713/72,160 alleles

Filtering AF 42.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 42%

Overall 22.4% 345,417/1,539,048 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	42.6%	2
Finnishnot grpmax-eligible	27.2%	4
Ashkenazi Jewishnot grpmax-eligible	26.1%	4
Middle Eastern	25.6%	4
Remaining individualsnot grpmax-eligible	22.8%	4
European (non-Finnish)	21.8%	5
South Asian	20.5%	5
Amishnot grpmax-eligible	18.8%	5
Admixed American	15.7%	6
East Asian	7.67%	13

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.Ser31=
Coding: c.93C>T
MANE Select: NM_001229
dbSNP: rs4645983
Type: single nucleotide variant
Location: chr1:15524108 (GRCh38)
Gene constraint: LOEUF 0.994 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.86 · 13 PDB
Residue 31: 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.Gln44Glu Benign ⚠ same condition
CASP9 p.Leu384= Likely benign same condition
CASP9 p.Leu8= Benign same condition
CASP9 p.Met157Val Likely 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-ser31 (accessed [today's date]).

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