Is CILP p.Arg493Trp (c.1477C>T) pathogenic?

CILP p.Arg493Trp (c.1477C>T) is classified Uncertain significance in CILP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-25). AlphaMissense: likely benign (0.1441); Ultra-rare (popmax 0.0164%, mid).

How common is CILP p.Arg493Trp (c.1477C>T) in the general population?

CILP p.Arg493Trp (c.1477C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about CILP p.Arg493Trp (c.1477C>T)?

AlphaMissense predicts likely benign (score 0.1441) — an in-silico prediction, not a clinical call.

CILP p.Arg493Trp

c.1477C>T · rs144548738 · VCV2295092

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1441 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1441	likely benign
REVEL	0.308	indeterminate
SaProt	LLR -9.82	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 0.65, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 13 kb · p 0.19 · regional, not allelic
Overall
CADD	25.0	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.0117% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0111%

Overall 0.0109% 176/1,614,024 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
European (non-Finnish)	0.0135%	7,422
Admixed American	0.0133%	7,502
Remaining individualsnot grpmax-eligible	0.0064%	15,622
East Asian	0.00445%	22,449
South Asian	0.0022%	45,546

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.Arg493Trp
Coding: c.1477C>T
MANE Select: NM_003613
dbSNP: rs144548738
Type: single nucleotide variant
Location: chr15:65198809 (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.Arg493Gln Uncertain significance ★ ⚠ same residue
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

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-arg493trp (accessed [today's date]).

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