Is IFT172 p.Arg720Pro (c.2159G>C) pathogenic?

IFT172 p.Arg720Pro (c.2159G>C) is classified Uncertain significance in IFT172 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-07-30). AlphaMissense: likely pathogenic (0.9163); Very rare (popmax 8.47e-05%, nfe); Associated with short-rib thoracic dysplasia 10 with or without polydactyly.

How common is IFT172 p.Arg720Pro (c.2159G>C) in the general population?

IFT172 p.Arg720Pro (c.2159G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about IFT172 p.Arg720Pro (c.2159G>C)?

AlphaMissense predicts likely pathogenic (score 0.9163) — an in-silico prediction, not a clinical call.

IFT172 p.Arg720Pro

Q: What condition is associated with IFT172 p.Arg720Pro (c.2159G>C)?

IFT172 p.Arg720Pro (c.2159G>C) is associated with short-rib thoracic dysplasia 10 with or without polydactyly, retinitis pigmentosa 71 (ClinVar).

c.2159G>C · rs202089120 · VCV1038486

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9163 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

short-rib thoracic dysplasia 10 with or without polydactyly

Computational evidence

Protein change
AlphaMissense	0.9163	likely pathogenic
REVEL	0.154	moderately benign-leaning
SaProt	LLR -12.97	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 32 kb · p 0.013 · regional, not allelic
Overall
CADD	24.2	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 8.47e-05% European (non-Finnish) · 1/1,180,038 alleles

Overall 6.2e-05% 1/1,614,180 alleles · very rare exomes 1/1,461,884 · genomes 0/152,296 · 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: IFT172
Protein: p.Arg720Pro
Coding: c.2159G>C
MANE Select: NM_015662
dbSNP: rs202089120
Type: single nucleotide variant
Location: chr2:27461793 (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.Arg720Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
IFT172 p.Arg720His Conflicting classifications of pathogenicity ★ ⚠ same residue
IFT172 p.Arg720fs Pathogenic/Likely pathogenic ★★ 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

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-arg720pro (accessed [today's date]).

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