Is CTIF p.Leu452Phe (c.1354C>T) pathogenic?

CTIF p.Leu452Phe (c.1354C>T) is classified Uncertain significance in CTIF (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-20). AlphaMissense: likely pathogenic (0.9469); Absent from gnomAD v4.1.

How common is CTIF p.Leu452Phe (c.1354C>T) in the general population?

CTIF p.Leu452Phe (c.1354C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTIF p.Leu452Phe (c.1354C>T)?

AlphaMissense predicts likely pathogenic (score 0.9469) — an in-silico prediction, not a clinical call.

CTIF p.Leu452Phe

c.1354C>T · rs1909009436 · VCV2238258

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9469 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9469	likely pathogenic
REVEL	0.48	indeterminate
SaProt	LLR -11.78	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 98 kb · p 1.5e-06 · regional, not allelic
Overall
CADD	29.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CTIF
Protein: p.Leu452Phe
Coding: c.1354C>T
MANE Select: NM_014772
dbSNP: rs1909009436
Type: single nucleotide variant
Location: chr18:48761672 (GRCh38)
Gene constraint: LOEUF 0.487 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 63.13
Residue 452: the mif4g domain

Full CTIF gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTIF c.326+4A>G Benign ★★ same type
CTIF p.Ala63= Benign ★★ same type
CTIF p.Ile277= Benign ★★ same type
CTIF c.1071+5C>T Uncertain significance ★ same type
CTIF p.Ala181Thr Uncertain significance ★ ⚠ same type
CTIF p.Ala271Val Uncertain significance ★ ⚠ same type
CTIF p.Ala304Thr Uncertain significance ★ ⚠ same type
CTIF p.Ala428Thr 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/ctif-p-leu452phe (accessed [today's date]).

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