Is CILP2 p.Arg388Trp (c.1162C>T) pathogenic?

CILP2 p.Arg388Trp (c.1162C>T) is classified Uncertain significance in CILP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-29). AlphaMissense: likely benign (0.0924); Very rare (popmax 0.00448%, eas).

How common is CILP2 p.Arg388Trp (c.1162C>T) in the general population?

CILP2 p.Arg388Trp (c.1162C>T) is very rare (popmax 0.00448%, eas) (gnomAD).

What do computational predictors say about CILP2 p.Arg388Trp (c.1162C>T)?

AlphaMissense predicts likely benign (score 0.0924) — an in-silico prediction, not a clinical call.

CILP2 p.Arg388Trp

c.1162C>T · VCV4229000

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0924 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00448%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0924	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -11.46	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -0.032, phastCons 0.001
Regional constraint	o/e 1.04	unconstrained · MANE · 7,663 bp · p 0.074 · regional, not allelic
Overall
CADD	20.9	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 0.00448% East Asian · 2/44,604 alleles

Filtering AF 0.000743% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000278%

Overall 0.000625% 10/1,599,494 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00448%	22,302
Admixed American	0.0017%	58,904
Remaining individualsnot grpmax-eligible	0.00162%	61,766
African / African-American	0.00134%	74,728
South Asian	0.00111%	89,764
European (non-Finnish)	0.000342%	292,662

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.Arg388Trp
Coding: c.1162C>T
MANE Select: NM_153221
Type: single nucleotide variant
Location: chr19:19543707 (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

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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-arg388trp (accessed [today's date]).

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