Is CILP p.Glu600Asp (c.1800A>T) pathogenic?

CILP p.Glu600Asp (c.1800A>T) is classified Uncertain significance in CILP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-18). AlphaMissense: ambiguous (0.3452); Ultra-rare (popmax 0.0165%, mid).

How common is CILP p.Glu600Asp (c.1800A>T) in the general population?

CILP p.Glu600Asp (c.1800A>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CILP p.Glu600Asp (c.1800A>T)?

AlphaMissense predicts ambiguous (score 0.3452) — an in-silico prediction, not a clinical call.

CILP p.Glu600Asp

c.1800A>T · VCV3833466

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3452 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3452	ambiguous
REVEL	0.172	moderately benign-leaning
SaProt	LLR -10.33	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.23	GERP -2.1, phastCons 0.35
Regional constraint	o/e 0.97	unconstrained · MANE · 13 kb · p 0.19 · regional, not allelic
Overall
CADD	19.63	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 0.0165% Middle Eastern · 1/6,062 alleles

Overall 6.84e-05% 1/1,461,894 alleles · ultra-rare

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.Glu600Asp
Coding: c.1800A>T
MANE Select: NM_003613
Type: single nucleotide variant
Location: chr15:65198486 (GRCh38)
Gene constraint: LOEUF 1.077 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.30

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-glu600asp (accessed [today's date]).

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