Is IFT80 p.Leu442= (c.1326C>T) pathogenic?

IFT80 p.Leu442= (c.1326C>T) is classified Conflicting classifications of pathogenicity in IFT80 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-07-05). Very rare (popmax 0.00134%, afr); Associated with Jeune syndrome.

What condition is associated with IFT80 p.Leu442= (c.1326C>T)?

IFT80 p.Leu442= (c.1326C>T) is associated with Jeune syndrome, asphyxiating thoracic dystrophy 2 (ClinVar).

How common is IFT80 p.Leu442= (c.1326C>T) in the general population?

IFT80 p.Leu442= (c.1326C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

IFT80 p.Leu442=

c.1326C>T · rs886058131 · VCV343968

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

Jeune syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.57	GERP -2.4, phastCons 0.99
Overall
CADD	2.903	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,800 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,610,552 alleles · very rare exomes 3/1,458,598 · genomes 1/151,954 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,800
European (non-Finnish)	0.000255%	392,519

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: IFT80
Protein: p.Leu442=
Coding: c.1326C>T
MANE Select: NM_020800
dbSNP: rs886058131
Type: single nucleotide variant
Location: chr3:160285858 (GRCh38)
Gene constraint: LOEUF 0.739 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.50

Full IFT80 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Jeune syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: asphyxiating thoracic dystrophy 2

Similar variants

IFT80 p.Arg495Ter Pathogenic/Likely pathogenic ★★ same condition
IFT80 p.Trp155Ter Pathogenic/Likely pathogenic ★★ same condition
IFT80 c.1076+6C>A Uncertain significance ★★ same condition
IFT80 c.1836+5T>C Uncertain significance ★★ same condition
IFT80 c.370+6T>C Uncertain significance ★★ same condition
IFT80 c.*108A>G Uncertain significance ★★ same condition
IFT80 p.Ala154Val Uncertain significance ★★ ⚠ same condition
IFT80 p.Ala236Val Uncertain significance ★★ ⚠ same condition

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/ift80-p-leu442 (accessed [today's date]).

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