Is CILP2 p.Arg88Cys (c.262C>T) pathogenic?

CILP2 p.Arg88Cys (c.262C>T) is classified Uncertain significance in CILP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-21). AlphaMissense: likely pathogenic (0.836); Very rare (popmax 8.54e-05%, nfe).

How common is CILP2 p.Arg88Cys (c.262C>T) in the general population?

CILP2 p.Arg88Cys (c.262C>T) is very rare (popmax 8.54e-05%, nfe) (gnomAD).

What do computational predictors say about CILP2 p.Arg88Cys (c.262C>T)?

AlphaMissense predicts likely pathogenic (score 0.836) — an in-silico prediction, not a clinical call.

CILP2 p.Arg88Cys

c.262C>T · rs2061238739 · VCV3145055

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.836 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.54e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.836	likely pathogenic
REVEL	0.402	indeterminate
SaProt	LLR -9.51	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP -3.7, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 7,663 bp · p 0.074 · regional, not allelic
Overall
CADD	27.9	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 8.54e-05% European (non-Finnish) · 1/1,170,966 alleles

Overall 6.97e-05% 1/1,434,686 alleles · very rare

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: CILP2
Protein: p.Arg88Cys
Coding: c.262C>T
MANE Select: NM_153221
dbSNP: rs2061238739
Type: single nucleotide variant
Location: chr19:19540302 (GRCh38)
Gene constraint: LOEUF 1.329 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.47

Full CILP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CILP2 p.Ala1022Val Uncertain significance ★ ⚠ same type
CILP2 p.Ala1044Val Uncertain significance ★ ⚠ same type
CILP2 p.Ala1045Val Uncertain significance ★ ⚠ same type
CILP2 p.Ala1076Val Uncertain significance ★ ⚠ same type
CILP2 p.Ala1096Val Uncertain significance ★ ⚠ same type
CILP2 p.Ala1109Val Uncertain significance ★ ⚠ same type
CILP2 p.Ala188Glu Uncertain significance ★ ⚠ same type
CILP2 p.Ala23Val 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/cilp2-p-arg88cys (accessed [today's date]).

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