Is CILP p.Ser359Arg (c.1075A>C) pathogenic?

CILP p.Ser359Arg (c.1075A>C) is classified Uncertain significance in CILP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-02). AlphaMissense: ambiguous (0.3533); Ultra-rare (popmax 0.0661%, eas).

How common is CILP p.Ser359Arg (c.1075A>C) in the general population?

CILP p.Ser359Arg (c.1075A>C) is ultra-rare (popmax 0.0661%, eas) (gnomAD).

What do computational predictors say about CILP p.Ser359Arg (c.1075A>C)?

AlphaMissense predicts ambiguous (score 0.3533) — an in-silico prediction, not a clinical call.

CILP p.Ser359Arg

c.1075A>C · rs775887125 · VCV2518525

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3533 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0661%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3533	ambiguous
REVEL	0.07	moderately benign-leaning
SaProt	LLR -8.26	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP -0.31, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 13 kb · p 0.19 · regional, not allelic
Overall
CADD	18.89	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 0.0661% East Asian · 29/43,880 alleles

Filtering AF 0.0473% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0408%

Overall 0.00212% 34/1,604,740 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0661%	1,513
Remaining individualsnot grpmax-eligible	0.00322%	31,060
European (non-Finnish)	0.000255%	392,009

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: CILP
Protein: p.Ser359Arg
Coding: c.1075A>C
MANE Select: NM_003613
dbSNP: rs775887125
Type: single nucleotide variant
Location: chr15:65201983 (GRCh38)
Gene constraint: LOEUF 1.077 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.30
Residue 359: a disulfide bond; the ig-like c2-type domain

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

Similar variants

CILP p.Leu1064= Benign ★★ same type
CILP p.Ala1003Asp Uncertain significance ★ ⚠ same type
CILP p.Ala102Val Uncertain significance ★ ⚠ same type
CILP p.Ala1053Thr Uncertain significance ★ ⚠ same type
CILP p.Ala1091Thr Uncertain significance ★ ⚠ same type
CILP p.Ala1091Val Uncertain significance ★ ⚠ same type
CILP p.Ala1114Gly Uncertain significance ★ ⚠ same type
CILP p.Ala1143Thr 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/cilp-p-ser359arg (accessed [today's date]).

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