Is CILP2 p.Arg606Trp (c.1816C>T) pathogenic?

CILP2 p.Arg606Trp (c.1816C>T) is classified Uncertain significance in CILP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-21). AlphaMissense: likely benign (0.1329); Very rare (popmax 0.0099%, sas).

How common is CILP2 p.Arg606Trp (c.1816C>T) in the general population?

CILP2 p.Arg606Trp (c.1816C>T) is very rare (popmax 0.0099%, sas) (gnomAD).

What do computational predictors say about CILP2 p.Arg606Trp (c.1816C>T)?

AlphaMissense predicts likely benign (score 0.1329) — an in-silico prediction, not a clinical call.

CILP2 p.Arg606Trp

c.1816C>T · rs768586017 · VCV2374572

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1329 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0099%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1329	likely benign
REVEL	0.173	moderately benign-leaning
SaProt	LLR -8.05	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 1.7	GERP -3.3, phastCons 0.96
Regional constraint	o/e 1.04	unconstrained · MANE · 7,663 bp · p 0.074 · regional, not allelic
Overall
CADD	23.6	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

Grpmax group 0.0099% South Asian · 9/90,896 alleles

Filtering AF 0.00515% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00376%

Overall 0.0018% 29/1,608,758 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0099%	10,100
East Asian	0.00447%	22,363
Remaining individualsnot grpmax-eligible	0.0016%	62,348
European (non-Finnish)	0.00144%	69,327

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.Arg606Trp
Coding: c.1816C>T
MANE Select: NM_153221
dbSNP: rs768586017
Type: single nucleotide variant
Location: chr19:19544361 (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-arg606trp (accessed [today's date]).

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