Is CILP2 p.Arg374Trp (c.1120C>T) pathogenic?

CILP2 p.Arg374Trp (c.1120C>T) is classified Likely benign in CILP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-25). AlphaMissense: likely benign (0.0632); Ultra-rare (popmax 0.0117%, amr).

How common is CILP2 p.Arg374Trp (c.1120C>T) in the general population?

CILP2 p.Arg374Trp (c.1120C>T) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about CILP2 p.Arg374Trp (c.1120C>T)?

AlphaMissense predicts likely benign (score 0.0632) — an in-silico prediction, not a clinical call.

CILP2 p.Arg374Trp

c.1120C>T · rs137913643 · VCV2458116

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0632 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0632	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -9.73	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 0.17	GERP -3.4
Regional constraint	o/e 1.04	unconstrained · MANE · 7,663 bp · p 0.074 · regional, not allelic
Overall
CADD	10.38	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 0.0117% Admixed American · 7/60,002 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00411%

Overall 0.00527% 85/1,613,118 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,572
Remaining individualsnot grpmax-eligible	0.0064%	15,619
European (non-Finnish)	0.00559%	17,879
African / African-American	0.00534%	18,734
South Asian	0.00329%	30,359
East Asian	0.00223%	44,890

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.Arg374Trp
Coding: c.1120C>T
MANE Select: NM_153221
dbSNP: rs137913643
Type: single nucleotide variant
Location: chr19:19543390 (GRCh38)
Gene constraint: LOEUF 1.329 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.47
Residue 374: the ig-like c2-type domain

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

Similar variants

CILP2 p.Arg374Gln Uncertain significance ★ ⚠ same residue
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

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-arg374trp (accessed [today's date]).

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