Is CILP2 p.Ala678Asp (c.2033C>A) pathogenic?

CILP2 p.Ala678Asp (c.2033C>A) is classified Uncertain significance in CILP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-08). AlphaMissense: likely benign (0.1119); Ultra-rare (popmax 0.0156%, nfe).

How common is CILP2 p.Ala678Asp (c.2033C>A) in the general population?

CILP2 p.Ala678Asp (c.2033C>A) is ultra-rare (popmax 0.0156%, nfe) (gnomAD).

What do computational predictors say about CILP2 p.Ala678Asp (c.2033C>A)?

AlphaMissense predicts likely benign (score 0.1119) — an in-silico prediction, not a clinical call.

CILP2 p.Ala678Asp

c.2033C>A · VCV3492978

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1119 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1119	likely benign
REVEL	0.157	moderately benign-leaning
SaProt	LLR -5.12	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 4.6	GERP 0.55, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 7,663 bp · p 0.074 · regional, not allelic
Overall
CADD	19.76	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 0.0156% European (non-Finnish) · 182/1,167,570 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.013%

Overall 0.0127% 201/1,576,512 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0156%	6,415
Remaining individualsnot grpmax-eligible	0.0147%	6,800
Admixed American	0.0123%	8,125
African / African-American	0.00404%	24,779

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.Ala678Asp
Coding: c.2033C>A
MANE Select: NM_153221
Type: single nucleotide variant
Location: chr19:19544578 (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.Ala678Thr 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-ala678asp (accessed [today's date]).

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