Is IFT80 p.Ser45Arg (c.135T>G) pathogenic?

IFT80 p.Ser45Arg (c.135T>G) is classified Uncertain significance in IFT80 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-20). AlphaMissense: ambiguous (0.3685); Very rare (popmax 0.000932%, nfe); Associated with asphyxiating thoracic dystrophy 2.

What condition is associated with IFT80 p.Ser45Arg (c.135T>G)?

IFT80 p.Ser45Arg (c.135T>G) is associated with asphyxiating thoracic dystrophy 2, Jeune syndrome (ClinVar).

How common is IFT80 p.Ser45Arg (c.135T>G) in the general population?

IFT80 p.Ser45Arg (c.135T>G) is very rare (popmax 0.000932%, nfe) (gnomAD).

What do computational predictors say about IFT80 p.Ser45Arg (c.135T>G)?

AlphaMissense predicts ambiguous (score 0.3685) — an in-silico prediction, not a clinical call.

IFT80 p.Ser45Arg

c.135T>G · rs762238566 · VCV1413580

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3685 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

asphyxiating thoracic dystrophy 2

Computational evidence

Protein change
AlphaMissense	0.3685	ambiguous
REVEL	0.152	moderately benign-leaning
SaProt	LLR -8.08	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP 0.65, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 126 kb · p 0.00011 · regional, not allelic
Overall
CADD	17.31	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000932% European (non-Finnish) · 11/1,179,878 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000682% 11/1,612,760 alleles · very rare exomes 6/1,460,610 · genomes 5/152,150 · 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.Ser45Arg
Coding: c.135T>G
MANE Select: NM_020800
dbSNP: rs762238566
Type: single nucleotide variant
Location: chr3:160381627 (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-ser45arg (accessed [today's date]).

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