Is IFT172 p.Phe53Ile (c.157T>A) pathogenic?

IFT172 p.Phe53Ile (c.157T>A) is classified Uncertain significance in IFT172 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-30). AlphaMissense: likely pathogenic (0.8195); Very rare (popmax 0.000169%, nfe); Associated with IFT172-related disorder.

What condition is associated with IFT172 p.Phe53Ile (c.157T>A)?

IFT172 p.Phe53Ile (c.157T>A) is associated with IFT172-related disorder (ClinVar).

How common is IFT172 p.Phe53Ile (c.157T>A) in the general population?

IFT172 p.Phe53Ile (c.157T>A) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about IFT172 p.Phe53Ile (c.157T>A)?

AlphaMissense predicts likely pathogenic (score 0.8195) — an in-silico prediction, not a clinical call.

IFT172 p.Phe53Ile

c.157T>A · rs776310391 · VCV2636702

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8195 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

IFT172-related disorder

Computational evidence

Protein change
AlphaMissense	0.8195	likely pathogenic
REVEL	0.365	indeterminate
SaProt	LLR -8.08	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 2.5, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 32 kb · p 0.013 · regional, not allelic
Overall
CADD	26.3	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 0.000169% European (non-Finnish) · 2/1,180,030 alleles

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

Overall 0.000124% 2/1,614,126 alleles · very rare exomes 2/1,461,850 · genomes 0/152,276 · 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.Phe53Ile
Coding: c.157T>A
MANE Select: NM_015662
dbSNP: rs776310391
Type: single nucleotide variant
Location: chr2:27485386 (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.Phe53Leu Uncertain significance ★ ⚠ same residue
IFT172 p.Phe53= Likely benign ★ 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

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-phe53ile (accessed [today's date]).

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