Is CASKIN2 p.Pro887Ser (c.2659C>T) pathogenic?

CASKIN2 p.Pro887Ser (c.2659C>T) is classified Uncertain significance in CASKIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). AlphaMissense: likely benign (0.0615); Absent from gnomAD v4.1.

How common is CASKIN2 p.Pro887Ser (c.2659C>T) in the general population?

CASKIN2 p.Pro887Ser (c.2659C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CASKIN2 p.Pro887Ser (c.2659C>T)?

AlphaMissense predicts likely benign (score 0.0615) — an in-silico prediction, not a clinical call.

CASKIN2 p.Pro887Ser

c.2659C>T · VCV4648426

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0615 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,461,552)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0615	likely benign
REVEL	0.006	strongly benign-leaning
SaProt	LLR -5.60	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 1.8	GERP -3.1, phastCons 0.97
Regional constraint	o/e 1.00	unconstrained · MANE · 4,779 bp · p 1 · regional, not allelic
Overall
CADD	1.863	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

No allele count reported in gnomAD v4.1 (AN 1,461,552). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CASKIN2
Protein: p.Pro887Ser
Coding: c.2659C>T
MANE Select: NM_020753
Type: single nucleotide variant
Location: chr17:75502415 (GRCh38)
Gene constraint: LOEUF 0.524 · pLI 0.41 (gnomAD)
Structure: AlphaFold pLDDT 58.59 · 4 PDB
Residue 887: the 'disordered' region

Full CASKIN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CASKIN2 c.1467+8C>A Benign ★★ same type
CASKIN2 p.Ala1005Glu Uncertain significance ★ ⚠ same type
CASKIN2 p.Ala1005Thr Uncertain significance ★ ⚠ same type
CASKIN2 p.Ala1087Gly Uncertain significance ★ ⚠ same type
CASKIN2 p.Ala1087Val Uncertain significance ★ ⚠ same type
CASKIN2 p.Ala1088Thr Uncertain significance ★ ⚠ same type
CASKIN2 p.Ala111Thr Uncertain significance ★ ⚠ same type
CASKIN2 p.Ala1120Val Uncertain significance ★ ⚠ 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/caskin2-p-pro887ser (accessed [today's date]).

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