Is IFT27 p.Pro52Leu (c.155C>T) pathogenic?

IFT27 p.Pro52Leu (c.155C>T) is classified Uncertain significance in IFT27 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-11). AlphaMissense: likely benign (0.1481); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with IFT27 p.Pro52Leu (c.155C>T)?

IFT27 p.Pro52Leu (c.155C>T) is associated with Inborn genetic diseases (ClinVar).

How common is IFT27 p.Pro52Leu (c.155C>T) in the general population?

IFT27 p.Pro52Leu (c.155C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IFT27 p.Pro52Leu (c.155C>T)?

AlphaMissense predicts likely benign (score 0.1481) — an in-silico prediction, not a clinical call.

IFT27 p.Pro52Leu

c.155C>T · VCV4621974

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1481 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1481	likely benign
REVEL	0.394	indeterminate
SaProt	LLR -9.91	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.4	GERP 0.11, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 17 kb · p 0.13 · regional, not allelic
Overall
CADD	23.9	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

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: IFT27
Protein: p.Pro52Leu
Coding: c.155C>T
MANE Select: NM_001177701
Type: single nucleotide variant
Location: chr22:36767325 (GRCh38)
Gene constraint: LOEUF 1.078 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.65

Full IFT27 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

IFT27 p.Arg26Cys Uncertain significance ★★ ⚠ same condition
IFT27 p.Lys3Gln Uncertain significance ★★ ⚠ same condition
IFT27 p.Asp53Asn Conflicting classifications of pathogenicity ★ ⚠ same condition
IFT27 p.Glu158Lys Uncertain significance ★ ⚠ same condition
IFT27 p.Ser27Gly Uncertain significance ★ ⚠ same condition
IFT27 p.Thr40Ile Uncertain significance ★ ⚠ same condition
IFT27 p.Val46Leu Conflicting classifications of pathogenicity ★ same condition
IFT27 p.Tyr36Cys Pathogenic ★★ 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/ift27-p-pro52leu (accessed [today's date]).

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