Is IFT80 p.Lys12= (c.36G>A) pathogenic?

IFT80 p.Lys12= (c.36G>A) is classified Uncertain significance in IFT80 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-11). Ultra-rare (popmax 0.0334%, afr); Associated with Jeune syndrome.

What condition is associated with IFT80 p.Lys12= (c.36G>A)?

IFT80 p.Lys12= (c.36G>A) is associated with Jeune syndrome (ClinVar).

How common is IFT80 p.Lys12= (c.36G>A) in the general population?

IFT80 p.Lys12= (c.36G>A) is ultra-rare (popmax 0.0334%, afr) (gnomAD).

IFT80 p.Lys12=

c.36G>A · rs764052178 · VCV1501701

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0334%, afr)

Conditions

Jeune syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.25	donor gain · deltas
Constraint at this position
Conservation	phyloP -0.22	GERP -2.9, phastCons 0.28
Overall
CADD	9.163	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0334% African / African-American · 24/71,868 alleles

Filtering AF 0.023% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0196%

Overall 0.00189% 28/1,485,012 alleles · ultra-rare exomes 14/1,333,022 · genomes 14/151,990 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0334%	2,994
Remaining individualsnot grpmax-eligible	0.00344%	29,093
Admixed American	0.00338%	29,584

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.Lys12=
Coding: c.36G>A
MANE Select: NM_020800
dbSNP: rs764052178
Type: single nucleotide variant
Location: chr3:160384565 (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

Similar variants

IFT80 p.Lys12Arg Uncertain significance ★ ⚠ same residue
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 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-lys12 (accessed [today's date]).

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