Is IFT52 p.Val53= (c.159G>A) pathogenic?

IFT52 p.Val53= (c.159G>A) is classified Benign in IFT52 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 79.8%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with short-rib thoracic dysplasia 16 with or without polydactyly.

What condition is associated with IFT52 p.Val53= (c.159G>A)?

IFT52 p.Val53= (c.159G>A) is associated with short-rib thoracic dysplasia 16 with or without polydactyly (ClinVar).

IFT52 p.Val53=

Q: How common is IFT52 p.Val53= (c.159G>A) in the general population?

IFT52 p.Val53= (c.159G>A) is common (popmax 79.8%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.159G>A · rs2664519 · VCV1183241

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 79.8%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

short-rib thoracic dysplasia 16 with or without polydactyly

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.65	GERP 0.82, phastCons 1
Overall
CADD	8.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 79.8% European (non-Finnish) · 935,903/1,172,116 alleles

Filtering AF 79.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 79.7%

Overall 78.7% 1,261,306/1,602,798 alleles · common exomes 1,146,803/1,450,628 · genomes 114,503/152,170 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	82.5%	1
Amishnot grpmax-eligible	81.9%	1
Ashkenazi Jewishnot grpmax-eligible	80.1%	1
European (non-Finnish)grpmax	79.8%	1
Middle Eastern	78.8%	1
Remaining individualsnot grpmax-eligible	77.7%	1
East Asian	77.6%	1
South Asian	77%	1
Admixed American	75.8%	1
African / African-American	62.6%	2

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val53=
Coding: c.159G>A
MANE Select: NM_016004
dbSNP: rs2664519
Type: single nucleotide variant
Location: chr20:43596474 (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 residue
IFT52 p.Pro397Ser Uncertain significance ★★ ⚠ 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-val53 (accessed [today's date]).

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