Is IFT52 p.Pro397Ser (c.1189C>T) pathogenic?

IFT52 p.Pro397Ser (c.1189C>T) is classified Uncertain significance in IFT52 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-04). AlphaMissense: likely benign (0.0982); Very rare (popmax 0.00801%, afr); Associated with short-rib thoracic dysplasia 16 with or without polydactyly.

What condition is associated with IFT52 p.Pro397Ser (c.1189C>T)?

IFT52 p.Pro397Ser (c.1189C>T) is associated with short-rib thoracic dysplasia 16 with or without polydactyly (ClinVar).

How common is IFT52 p.Pro397Ser (c.1189C>T) in the general population?

IFT52 p.Pro397Ser (c.1189C>T) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about IFT52 p.Pro397Ser (c.1189C>T)?

AlphaMissense predicts likely benign (score 0.0982) — an in-silico prediction, not a clinical call.

IFT52 p.Pro397Ser

c.1189C>T · rs764053825 · VCV1683682

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0982 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

short-rib thoracic dysplasia 16 with or without polydactyly

Computational evidence

Protein change
AlphaMissense	0.0982	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -11.45	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 52 kb · p 0.0018 · regional, not allelic
Overall
CADD	21.5	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 0.00801% African / African-American · 6/74,902 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.000434% 7/1,613,998 alleles · very rare exomes 3/1,461,846 · genomes 4/152,152 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,484
Admixed American	0.00167%	59,982

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: IFT52
Protein: p.Pro397Ser
Coding: c.1189C>T
MANE Select: NM_016004
dbSNP: rs764053825
Type: single nucleotide variant
Location: chr20:43642547 (GRCh38)
Gene constraint: LOEUF 1.116 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.21

Full IFT52 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

short-rib thoracic dysplasia 16 with or without polydactyly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

IFT52 p.Val53Met Uncertain significance ★★ ⚠ same condition
IFT52 p.Val53= Benign ★★ same condition
IFT52 p.Ala199Thr Likely pathogenic ★ same condition
IFT52 p.Arg142Ter Pathogenic ★ same condition
IFT52 p.Trp239Ter Likely pathogenic ★ same condition
IFT52 p.Asn98Ser Pathogenic ⚠ same condition
IFT52 p.Thr186Ala Pathogenic ⚠ same condition
IFT52 p.Ile232_Met233delinsThr 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/ift52-p-pro397ser (accessed [today's date]).

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