Is IFT80 p.Ile368= (c.1104A>T) pathogenic?

IFT80 p.Ile368= (c.1104A>T) is classified Conflicting classifications of pathogenicity in IFT80 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-14). Ultra-rare (popmax 0.0373%, afr); Associated with asphyxiating thoracic dystrophy 2.

What condition is associated with IFT80 p.Ile368= (c.1104A>T)?

IFT80 p.Ile368= (c.1104A>T) is associated with asphyxiating thoracic dystrophy 2, Jeune syndrome (ClinVar).

How common is IFT80 p.Ile368= (c.1104A>T) in the general population?

IFT80 p.Ile368= (c.1104A>T) is ultra-rare (popmax 0.0373%, afr) (gnomAD).

IFT80 p.Ile368=

c.1104A>T · rs369114064 · VCV900395

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0373%, afr)

Conditions

asphyxiating thoracic dystrophy 2

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 2.3	GERP 0.29, phastCons 1
Overall
CADD	10.35	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0373% African / African-American · 28/74,992 alleles

Filtering AF 0.0265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0229%

Overall 0.00254% 41/1,611,388 alleles · ultra-rare exomes 24/1,459,056 · genomes 17/152,332 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0373%	2,678
Admixed American	0.0117%	8,573
Remaining individualsnot grpmax-eligible	0.00641%	15,602
South Asian	0.0011%	90,982
European (non-Finnish)	8.49e-05%	1,177,794

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.Ile368=
Coding: c.1104A>T
MANE Select: NM_020800
dbSNP: rs369114064
Type: single nucleotide variant
Location: chr3:160303962 (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

asphyxiating thoracic dystrophy 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Jeune syndrome

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-ile368 (accessed [today's date]).

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