Is CILP2 p.Ser1113Arg (c.3339C>A) pathogenic?

CILP2 p.Ser1113Arg (c.3339C>A) is classified Uncertain significance in CILP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-13). AlphaMissense: likely pathogenic (0.789); Ultra-rare (popmax 0.0169%, mid).

How common is CILP2 p.Ser1113Arg (c.3339C>A) in the general population?

CILP2 p.Ser1113Arg (c.3339C>A) is ultra-rare (popmax 0.0169%, mid) (gnomAD).

What do computational predictors say about CILP2 p.Ser1113Arg (c.3339C>A)?

AlphaMissense predicts likely pathogenic (score 0.789) — an in-silico prediction, not a clinical call.

CILP2 p.Ser1113Arg

c.3339C>A · rs2513916556 · VCV3145064

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.789 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0169%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.789	likely pathogenic
REVEL	0.204	benign-leaning
SaProt	LLR -8.19	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP 0.54, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 7,663 bp · p 0.074 · regional, not allelic
Overall
CADD	23.2	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 0.0169% Middle Eastern · 1/5,930 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000209% 3/1,435,898 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0169%	5,930
European (non-Finnish)	0.000172%	580,987

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.Ser1113Arg
Coding: c.3339C>A
MANE Select: NM_153221
dbSNP: rs2513916556
Type: single nucleotide variant
Location: chr19:19545884 (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-ser1113arg (accessed [today's date]).

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