Is IFT80 p.Ala739= (c.2217A>G) pathogenic?

IFT80 p.Ala739= (c.2217A>G) is classified Uncertain significance in IFT80 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-29). Very rare (popmax 8.49e-05%, nfe); Associated with asphyxiating thoracic dystrophy 2.

What condition is associated with IFT80 p.Ala739= (c.2217A>G)?

IFT80 p.Ala739= (c.2217A>G) is associated with asphyxiating thoracic dystrophy 2 (ClinVar).

How common is IFT80 p.Ala739= (c.2217A>G) in the general population?

IFT80 p.Ala739= (c.2217A>G) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

IFT80 p.Ala739=

c.2217A>G · VCV3588715

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

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 1.9	phastCons 1
Overall
CADD	7.742	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,178,500 alleles

Overall 6.2e-05% 1/1,612,336 alleles · very rare exomes 1/1,459,974 · genomes 0/152,362 · joint denominator

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.Ala739=
Coding: c.2217A>G
MANE Select: NM_020800
Type: single nucleotide variant
Location: chr3:160268419 (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

Similar variants

IFT80 p.Arg495Ter 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.Ala236Val Uncertain significance ★★ ⚠ same condition
IFT80 p.Arg220Cys Uncertain significance ★★ ⚠ same condition
IFT80 p.Arg220His 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-ala739 (accessed [today's date]).

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