Is IFT81 p.Arg481Ter (c.1441C>T) pathogenic?

IFT81 p.Arg481Ter (c.1441C>T) is classified Pathogenic/Likely pathogenic in IFT81 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-04-17). Ultra-rare (popmax 0.0188%, afr); Associated with IFT81-related disorders.

What condition is associated with IFT81 p.Arg481Ter (c.1441C>T)?

IFT81 p.Arg481Ter (c.1441C>T) is associated with IFT81-related disorders, short-rib thoracic dysplasia 19 with or without polydactyly (ClinVar).

How common is IFT81 p.Arg481Ter (c.1441C>T) in the general population?

IFT81 p.Arg481Ter (c.1441C>T) is ultra-rare (popmax 0.0188%, afr) (gnomAD).

IFT81 p.Arg481Ter

c.1441C>T · rs201791587 · VCV956773

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0188%, afr)

Conditions

IFT81-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 13 of 19
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 2.3, phastCons 1
Overall
CADD	38.0	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 0.0188% African / African-American · 14/74,594 alleles

Filtering AF 0.0113% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00908%

Overall 0.00392% 63/1,607,900 alleles · ultra-rare exomes 56/1,455,960 · genomes 7/151,940 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0188%	5,328
South Asian	0.0078%	12,821
European (non-Finnish)	0.00323%	30,994
Remaining individualsnot grpmax-eligible	0.00321%	31,111
East Asian	0.00225%	44,528
Admixed American	0.00169%	59,080

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.Arg481Ter
Coding: c.1441C>T
MANE Select: NM_014055
dbSNP: rs201791587
Type: single nucleotide variant
Location: chr12:110191022 (GRCh38)
Gene constraint: LOEUF 1.054 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.45
Residue 481: a UniProt-annotated variant site (in srtd19)

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

Disease context

IFT81-related disorders

Also linked: short-rib thoracic dysplasia 19 with or without polydactyly

Similar variants

IFT81 p.Arg481Gln Uncertain significance ★ ⚠ same residue
IFT81 p.Arg481= Likely benign ★ same residue
IFT81 c.1717-2A>G Pathogenic/Likely pathogenic ★★ same condition
IFT81 c.249-1G>A Pathogenic/Likely pathogenic ★★ same condition
IFT81 p.Arg213Ter Pathogenic/Likely pathogenic ★★ same condition
IFT81 p.Arg399Ter Pathogenic/Likely pathogenic ★★ same condition
IFT81 p.Arg512Ter Pathogenic/Likely pathogenic ★★ same condition
IFT81 p.Arg64Ter Pathogenic ★★ 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-arg481ter (accessed [today's date]).

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