Is TP73 p.Thr173= (c.519C>T) pathogenic?

TP73 p.Thr173= (c.519C>T) is classified Benign in TP73 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-11). Common (popmax 92.3%, mid) — too common for a highly-penetrant pathogenic allele; Associated with ciliary dyskinesia, primary, 47, and lissencephaly.

What condition is associated with TP73 p.Thr173= (c.519C>T)?

TP73 p.Thr173= (c.519C>T) is associated with ciliary dyskinesia, primary, 47, and lissencephaly (ClinVar).

How is Primary ciliary dyskinesia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

TP73 p.Thr173=

Q: How common is TP73 p.Thr173= (c.519C>T) in the general population?

TP73 p.Thr173= (c.519C>T) is common (popmax 92.3%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.519C>T · rs1801174 · VCV2585656

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 92.3%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

ciliary dyskinesia, primary, 47, and lissencephaly

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 -12	GERP -4.7
Overall
CADD	2.09	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 92.3% Middle Eastern · 5,590/6,056 alleles

Filtering AF 90.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 89.5%

Overall 86% 1,386,232/1,612,596 alleles · common exomes 1,260,594/1,460,388 · genomes 125,638/152,208 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	97.5%	1
Ashkenazi Jewishnot grpmax-eligible	92.9%	1
Middle Easterngrpmax	92.3%	1
European (non-Finnish)	89.5%	1
Remaining individualsnot grpmax-eligible	85.5%	1
Finnishnot grpmax-eligible	85.4%	1
African / African-American	76.8%	1
South Asian	75.9%	1
Admixed American	66.3%	2
East Asian	51.1%	2

Amish 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: TP73
Protein: p.Thr173=
Coding: c.519C>T
MANE Select: NM_005427
dbSNP: rs1801174
Type: single nucleotide variant
Location: chr1:3722110 (GRCh38)
Gene constraint: LOEUF 0.576 · pLI 0.29 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.25 · 28 PDB
Residue 173: the 'dna-binding' region

Full TP73 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ciliary dyskinesia, primary, 47, and lissencephaly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

TP73 p.Arg538Cys Uncertain significance ★★ ⚠ same condition
TP73 c.1196+1G>A Pathogenic ★ same condition
TP73 p.Glu205Ter Pathogenic ★ same condition
TP73 p.Arg591Cys Uncertain significance ★ ⚠ same condition
TP73 p.Gly464= Uncertain significance ★ same condition
TP73 p.Val448Met Uncertain significance ★ ⚠ same condition
TP73 c.985+15A>G Benign ★ same condition
TP73 c.-20C>T Benign ★ 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/tp73-p-thr173 (accessed [today's date]).

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