Is CILP p.Val135Ile (c.403G>A) pathogenic?

CILP p.Val135Ile (c.403G>A) is classified Uncertain significance in CILP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-29). AlphaMissense: likely benign (0.1013); Ultra-rare (popmax 0.0133%, afr).

How common is CILP p.Val135Ile (c.403G>A) in the general population?

CILP p.Val135Ile (c.403G>A) is ultra-rare (popmax 0.0133%, afr) (gnomAD).

What do computational predictors say about CILP p.Val135Ile (c.403G>A)?

AlphaMissense predicts likely benign (score 0.1013) — an in-silico prediction, not a clinical call.

CILP p.Val135Ile

c.403G>A · VCV3833453

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1013 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1013	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -8.11	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 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 13 kb · p 0.19 · regional, not allelic
Overall
CADD	22.4	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 0.0133% African / African-American · 10/74,980 alleles

Filtering AF 0.00722% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00549%

Overall 0.0013% 21/1,612,932 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0133%	7,498
Admixed American	0.005%	20,000
East Asian	0.00223%	44,828
South Asian	0.0011%	91,044
European (non-Finnish)	0.000509%	196,538

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.Val135Ile
Coding: c.403G>A
MANE Select: NM_003613
Type: single nucleotide variant
Location: chr15:65206803 (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.Val135Leu 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-val135ile (accessed [today's date]).

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