Is IFT172 p.Arg755Pro (c.2264G>C) pathogenic?

IFT172 p.Arg755Pro (c.2264G>C) is classified Uncertain significance in IFT172 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-03-26). AlphaMissense: ambiguous (0.5502); Very rare (popmax 0.00602%, nfe); Associated with Inborn genetic diseases.

What condition is associated with IFT172 p.Arg755Pro (c.2264G>C)?

IFT172 p.Arg755Pro (c.2264G>C) is associated with Inborn genetic diseases, short-rib thoracic dysplasia 10 with or without polydactyly, retinitis pigmentosa 71 (ClinVar).

How common is IFT172 p.Arg755Pro (c.2264G>C) in the general population?

IFT172 p.Arg755Pro (c.2264G>C) is very rare (popmax 0.00602%, nfe) (gnomAD).

What do computational predictors say about IFT172 p.Arg755Pro (c.2264G>C)?

AlphaMissense predicts ambiguous (score 0.5502) — an in-silico prediction, not a clinical call.

IFT172 p.Arg755Pro

c.2264G>C · rs78631901 · VCV958328

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.5502 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00602%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5502	ambiguous
REVEL	0.239	benign-leaning
SaProt	LLR -11.34	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.85	GERP 2.2, phastCons 0.33
Regional constraint	o/e 0.93	unconstrained · MANE · 32 kb · p 0.013 · regional, not allelic
Overall
CADD	24.0	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 0.00602% European (non-Finnish) · 71/1,180,026 alleles

Filtering AF 0.00486% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00447%

Overall 0.00477% 77/1,614,036 alleles · very rare exomes 73/1,461,882 · genomes 4/152,154 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00602%	16,620
Admixed American	0.005%	20,003
Remaining individualsnot grpmax-eligible	0.0032%	31,243
African / African-American	0.00133%	74,912

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.Arg755Pro
Coding: c.2264G>C
MANE Select: NM_015662
dbSNP: rs78631901
Type: single nucleotide variant
Location: chr2:27461447 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: short-rib thoracic dysplasia 10 with or without polydactyly retinitis pigmentosa 71 Bardet-Biedl syndrome 20

Similar variants

IFT172 p.Arg755Gln Likely benign ★★ 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-arg755pro (accessed [today's date]).

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