Is IFT81 p.Asp672fs (c.2015_2019del) pathogenic?

IFT81 p.Asp672fs (c.20152019del) is classified Uncertain significance in IFT81 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-03-17). Rare (popmax 0.155%, mid); Associated with short-rib thoracic dysplasia 19 with or without polydactyly.

What condition is associated with IFT81 p.Asp672fs (c.2015_2019del)?

IFT81 p.Asp672fs (c.2015_2019del) is associated with short-rib thoracic dysplasia 19 with or without polydactyly, ciliopathy (ClinVar).

How common is IFT81 p.Asp672fs (c.2015_2019del) in the general population?

IFT81 p.Asp672fs (c.2015_2019del) is rare (popmax 0.155%, mid) (gnomAD).

IFT81 p.Asp672fs

c.2015_2019del · rs864309658 · VCV218893

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.155%, mid)

Conditions

short-rib thoracic dysplasia 19 with or without polydactyly

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (19 of 19) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.4	GERP 2.5, phastCons 1
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.155% Middle Eastern · 9/5,794 alleles

Filtering AF 0.081% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0605%

Overall 0.00422% 66/1,562,968 alleles · rare exomes 61/1,410,686 · genomes 5/152,282 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.155%	644
East Asian	0.0362%	2,764
Remaining individualsnot grpmax-eligible	0.0149%	6,696
European (non-Finnish)	0.00267%	37,467
Admixed American	0.00206%	48,478

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: IFT81
Protein: p.Asp672fs
Coding: c.2015_2019del
MANE Select: NM_014055
dbSNP: rs864309658
Type: Deletion
Location: chr12:110218208 (GRCh38)
Gene constraint: LOEUF 1.054 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.45
Residue 672: a UniProt-annotated variant site (in srtd19)

Full IFT81 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

short-rib thoracic dysplasia 19 with or without polydactyly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ciliopathy

Similar variants

IFT81 p.Asp672Gly Uncertain significance ★★ ⚠ same residue
IFT81 p.Leu154fs Likely pathogenic ★ same condition
IFT81 c.1717-2A>G Pathogenic/Likely pathogenic ★★ same condition
IFT81 p.Arg481Ter Pathogenic/Likely pathogenic ★★ same condition
IFT81 p.Arg512Ter Pathogenic/Likely pathogenic ★★ same condition
IFT81 p.Arg64Ter Pathogenic ★★ same condition
IFT81 p.Leu29Phe Pathogenic/Likely pathogenic ★★ ⚠ same condition
IFT81 p.His306Leu 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/ift81-p-asp672fs (accessed [today's date]).

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