Is CASP8 p.Ser4Gly (c.10A>G) pathogenic?

CASP8 p.Ser4Gly (c.10A>G) is classified Uncertain significance in CASP8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-22). AlphaMissense: likely benign (0.0772); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CASP8 p.Ser4Gly (c.10A>G)?

CASP8 p.Ser4Gly (c.10A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CASP8 p.Ser4Gly (c.10A>G) in the general population?

CASP8 p.Ser4Gly (c.10A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CASP8 p.Ser4Gly (c.10A>G)?

AlphaMissense predicts likely benign (score 0.0772) — an in-silico prediction, not a clinical call.

CASP8 p.Ser4Gly

c.10A>G · VCV3827562

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0772 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0772	likely benign
REVEL	0.247	benign-leaning
SaProt	LLR -7.93	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 0.9	GERP -2.5, phastCons 0.017
Regional constraint	o/e 0.82	unconstrained · MANE · 20 kb · p 2.8e-05 · regional, not allelic
Overall
CADD	4.43	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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: CASP8
Protein: p.Ser4Gly
Coding: c.10A>G
MANE Select: NM_001372051
Type: single nucleotide variant
Location: chr2:201266496 (GRCh38)
Gene constraint: LOEUF 0.695 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.37 · 36 PDB
Residue 4: the ded 1 domain; an α-helix

Full CASP8 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

Similar variants

CASP8 c.306-1926A>G Uncertain significance ★★ same condition
CASP8 c.306-1935G>A Uncertain significance ★★ same condition
CASP8 p.Arg233Trp Uncertain significance ★★ ⚠ same condition
CASP8 p.Asp223Asn Uncertain significance ★★ ⚠ same condition
CASP8 p.Cys236Arg Uncertain significance ★★ ⚠ same condition
CASP8 p.Glu84Gly Uncertain significance ★★ ⚠ same condition
CASP8 p.Gly350Arg Uncertain significance ★★ ⚠ same condition
CASP8 p.Lys23Arg 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-ser4gly (accessed [today's date]).

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