Is IFT80 p.Ile60Val (c.178A>G) pathogenic?

IFT80 p.Ile60Val (c.178A>G) is classified Uncertain significance in IFT80 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-02). AlphaMissense: likely benign (0.0626); Very rare (popmax 0.00167%, amr); Associated with Jeune syndrome.

What condition is associated with IFT80 p.Ile60Val (c.178A>G)?

IFT80 p.Ile60Val (c.178A>G) is associated with Jeune syndrome (ClinVar).

How common is IFT80 p.Ile60Val (c.178A>G) in the general population?

IFT80 p.Ile60Val (c.178A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about IFT80 p.Ile60Val (c.178A>G)?

AlphaMissense predicts likely benign (score 0.0626) — an in-silico prediction, not a clinical call.

IFT80 p.Ile60Val

c.178A>G · rs780018349 · VCV1409243

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0626 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Jeune syndrome

Computational evidence

Protein change
AlphaMissense	0.0626	likely benign
REVEL	0.155	moderately benign-leaning
SaProt	LLR -6.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 0.63, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 126 kb · p 0.00011 · regional, not allelic
Overall
CADD	17.06	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

Grpmax group 0.00167% Admixed American · 1/59,976 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000558% 9/1,613,602 alleles · very rare exomes 7/1,461,530 · genomes 2/152,072 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,976
African / African-American	0.00134%	74,882
European (non-Finnish)	0.000593%	168,558

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.Ile60Val
Coding: c.178A>G
MANE Select: NM_020800
dbSNP: rs780018349
Type: single nucleotide variant
Location: chr3:160381584 (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.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
IFT80 p.Arg220Cys 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-ile60val (accessed [today's date]).

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