Is CILP p.Thr49Ile (c.146C>T) pathogenic?

CILP p.Thr49Ile (c.146C>T) is classified Likely benign in CILP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-29). AlphaMissense: likely benign (0.0697); Rare (popmax 0.137%, afr).

How common is CILP p.Thr49Ile (c.146C>T) in the general population?

CILP p.Thr49Ile (c.146C>T) is rare (popmax 0.137%, afr) (gnomAD).

What do computational predictors say about CILP p.Thr49Ile (c.146C>T)?

AlphaMissense predicts likely benign (score 0.0697) — an in-silico prediction, not a clinical call.

CILP p.Thr49Ile

c.146C>T · VCV4228965

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0697 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.137%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0697	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -6.85	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 3.3	GERP -0.92, phastCons 0.39
Regional constraint	o/e 0.97	unconstrained · MANE · 13 kb · p 0.19 · regional, not allelic
Overall
CADD	4.754	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 0.137% African / African-American · 103/75,044 alleles

Filtering AF 0.116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.108%

Overall 0.00892% 144/1,614,070 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.137%	729
Admixed American	0.035%	2,859
Remaining individualsnot grpmax-eligible	0.024%	4,167
South Asian	0.0022%	45,531
European (non-Finnish)	0.000254%	393,315

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.Thr49Ile
Coding: c.146C>T
MANE Select: NM_003613
Type: single nucleotide variant
Location: chr15:65207680 (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-thr49ile (accessed [today's date]).

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