Is IFT80 p.Arg609Cys (c.1825C>T) pathogenic?

IFT80 p.Arg609Cys (c.1825C>T) is classified Uncertain significance in IFT80 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-07). AlphaMissense: likely benign (0.2516); Ultra-rare (popmax 0.0165%, mid); Associated with asphyxiating thoracic dystrophy 2.

What condition is associated with IFT80 p.Arg609Cys (c.1825C>T)?

IFT80 p.Arg609Cys (c.1825C>T) is associated with asphyxiating thoracic dystrophy 2 (ClinVar).

How common is IFT80 p.Arg609Cys (c.1825C>T) in the general population?

IFT80 p.Arg609Cys (c.1825C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about IFT80 p.Arg609Cys (c.1825C>T)?

AlphaMissense predicts likely benign (score 0.2516) — an in-silico prediction, not a clinical call.

IFT80 p.Arg609Cys

c.1825C>T · rs186192085 · VCV194670

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2516 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

asphyxiating thoracic dystrophy 2

Computational evidence

Protein change
AlphaMissense	0.2516	likely benign
REVEL	0.553	indeterminate
SaProt	LLR -13.30	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.27	donor gain · deltas
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 126 kb · p 0.00011 · regional, not allelic
Overall
CADD	33.0	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 0.0165% Middle Eastern · 1/6,058 alleles

Filtering AF 0.00429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00112% 18/1,612,628 alleles · ultra-rare exomes 14/1,460,578 · genomes 4/152,050 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,058
Admixed American	0.01%	9,992
East Asian	0.00223%	44,842
South Asian	0.0022%	45,509
Finnishnot grpmax-eligible	0.00156%	63,952
African / African-American	0.00133%	74,914
European (non-Finnish)	0.000509%	196,490

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.Arg609Cys
Coding: c.1825C>T
MANE Select: NM_020800
dbSNP: rs186192085
Type: single nucleotide variant
Location: chr3:160279204 (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-arg609cys (accessed [today's date]).

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