Is IFT172 p.Arg658Ter (c.1972C>T) pathogenic?

IFT172 p.Arg658Ter (c.1972C>T) is classified Pathogenic in IFT172 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-17). Very rare (popmax 0.000169%, nfe); Associated with short-rib thoracic dysplasia 10 with or without polydactyly.

How common is IFT172 p.Arg658Ter (c.1972C>T) in the general population?

IFT172 p.Arg658Ter (c.1972C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

IFT172 p.Arg658Ter

Q: What condition is associated with IFT172 p.Arg658Ter (c.1972C>T)?

IFT172 p.Arg658Ter (c.1972C>T) is associated with short-rib thoracic dysplasia 10 with or without polydactyly, retinitis pigmentosa 71 (ClinVar).

c.1972C>T · rs1553329745 · VCV2930886

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

short-rib thoracic dysplasia 10 with or without polydactyly

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 19 of 48
Splicing
SpliceAI	Δ0.23	donor loss, 50 bp away · masked 0 · deltas
Pangolin	Δ0.50	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 9.8	GERP 2.2, phastCons 1
Overall
CADD	37.0	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 0.000169% European (non-Finnish) · 2/1,180,044 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,972 alleles · very rare

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: IFT172
Protein: p.Arg658Ter
Coding: c.1972C>T
MANE Select: NM_015662
dbSNP: rs1553329745
Type: single nucleotide variant
Location: chr2:27463147 (GRCh38)
Gene constraint: LOEUF 0.745 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.98 · 1 PDB

Full IFT172 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

short-rib thoracic dysplasia 10 with or without polydactyly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa 71

Similar variants

IFT172 p.Arg658Gln Uncertain significance ★★ ⚠ same residue
IFT172 c.1411+2T>C Likely pathogenic ★★ same condition
IFT172 c.1525-1G>A Pathogenic/Likely pathogenic ★★ same condition
IFT172 c.184-2A>C Likely pathogenic ★★ same condition
IFT172 c.2443-1G>C Likely pathogenic ★★ same condition
IFT172 c.2976-2A>T Likely pathogenic ★★ same condition
IFT172 c.3111+1G>T Likely pathogenic ★★ same condition
IFT172 c.3821+1G>A Pathogenic/Likely 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/ift172-p-arg658ter (accessed [today's date]).

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