Is IFT172 p.Arg451Pro (c.1352G>C) pathogenic?

IFT172 p.Arg451Pro (c.1352G>C) is classified Uncertain significance in IFT172 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-10). AlphaMissense: likely benign (0.1968); Very rare (popmax 0.0011%, nfe); Associated with IFT172-related disorder.

What condition is associated with IFT172 p.Arg451Pro (c.1352G>C)?

IFT172 p.Arg451Pro (c.1352G>C) is associated with IFT172-related disorder (ClinVar).

How common is IFT172 p.Arg451Pro (c.1352G>C) in the general population?

IFT172 p.Arg451Pro (c.1352G>C) is very rare (popmax 0.0011%, nfe) (gnomAD).

What do computational predictors say about IFT172 p.Arg451Pro (c.1352G>C)?

AlphaMissense predicts likely benign (score 0.1968) — an in-silico prediction, not a clinical call.

IFT172 p.Arg451Pro

c.1352G>C · rs753504432 · VCV2628730

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1968 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

IFT172-related disorder

Computational evidence

Protein change
AlphaMissense	0.1968	likely benign
REVEL	0.218	benign-leaning
SaProt	LLR -4.85	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.27	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 0.23	GERP -4.3, phastCons 0.97
Regional constraint	o/e 0.93	unconstrained · MANE · 32 kb · p 0.013 · regional, not allelic
Overall
CADD	18.66	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% European (non-Finnish) · 13/1,178,752 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000806% 13/1,612,596 alleles · very rare exomes 13/1,460,364 · genomes 0/152,232 · 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.Arg451Pro
Coding: c.1352G>C
MANE Select: NM_015662
dbSNP: rs753504432
Type: single nucleotide variant
Location: chr2:27476700 (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

IFT172-related disorder

Similar variants

IFT172 p.Arg451Gln Uncertain significance ★★ ⚠ same residue
IFT172 c.1525-1G>A Pathogenic/Likely pathogenic ★★ same condition
IFT172 c.184-2A>C Likely pathogenic ★★ same condition
IFT172 c.786-2A>G Likely pathogenic ★★ same condition
IFT172 p.Arg346Ter Pathogenic/Likely pathogenic ★★ same condition
IFT172 p.Arg38Ter Pathogenic/Likely pathogenic ★★ same condition
IFT172 p.Arg685Ter Pathogenic/Likely pathogenic ★★ same condition
IFT172 p.Arg789Ter 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-arg451pro (accessed [today's date]).

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