Is CASP8 p.Ser113= (c.339C>T) pathogenic?

CASP8 p.Ser113= (c.339C>T) is classified Benign/Likely benign in CASP8 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-04-06). Rare (popmax 0.428%, nfe); Associated with hereditary breast carcinoma.

What condition is associated with CASP8 p.Ser113= (c.339C>T)?

CASP8 p.Ser113= (c.339C>T) is associated with hereditary breast carcinoma, hepatocellular carcinoma, lung cancer (ClinVar).

How common is CASP8 p.Ser113= (c.339C>T) in the general population?

CASP8 p.Ser113= (c.339C>T) is rare (popmax 0.428%, nfe) (gnomAD).

How is Hereditary breast cancer inherited?

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

CASP8 p.Ser113=

c.339C>T · rs17860422 · VCV333498

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.428%, nfe)

Conditions

hereditary breast carcinoma

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
Pangolin	Δ0.20	loss · gain 0.04 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP -1.1	GERP -3.1
Overall
CADD	1.528	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.428% European (non-Finnish) · 5,030/1,174,764 alleles

Filtering AF 0.418% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.414%

Overall 0.372% 5,987/1,608,458 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.428%	234
Admixed American	0.4%	250
Remaining individualsnot grpmax-eligible	0.329%	304
Finnishnot grpmax-eligible	0.256%	390
South Asian	0.252%	397
Ashkenazi Jewishnot grpmax-eligible	0.189%	528
Middle Eastern	0.182%	550
Amishnot grpmax-eligible	0.11%	912
African / African-American	0.068%	1,470

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: CASP8
Protein: p.Ser113=
Coding: c.339C>T
MANE Select: NM_001372051
dbSNP: rs17860422
Type: single nucleotide variant
Location: chr2:201271549 (GRCh38)
Gene constraint: LOEUF 0.695 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.37 · 36 PDB
Residue 113: the ded 2 domain

Full CASP8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary breast carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hepatocellular carcinoma lung cancer autoimmune lymphoproliferative syndrome type 2B

For Hereditary breast cancer (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial
Onset: Adult, Elderly

Similar variants

CASP8 p.Arg248Trp Pathogenic/Likely pathogenic ★★ same condition
CASP8 c.306-1926A>G Uncertain significance ★★ same condition
CASP8 c.306-1935G>A Uncertain significance ★★ same condition
CASP8 c.306-1971A>G Uncertain significance ★★ same condition
CASP8 c.660+6C>T Uncertain significance ★★ same condition
CASP8 c.*107C>T Uncertain significance ★★ same condition
CASP8 p.Ala96Ser Uncertain significance ★★ ⚠ same condition
CASP8 p.Arg233Trp 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/casp8-p-ser113 (accessed [today's date]).

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