Is PITX3 p.Pro210= (c.630A>C) pathogenic?

PITX3 p.Pro210= (c.630A>C) is classified Likely benign in PITX3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-06-17). Ultra-rare (popmax 0.0147%, nfe); Associated with PITX3-related disorder.

What condition is associated with PITX3 p.Pro210= (c.630A>C)?

PITX3 p.Pro210= (c.630A>C) is associated with PITX3-related disorder (ClinVar).

How common is PITX3 p.Pro210= (c.630A>C) in the general population?

PITX3 p.Pro210= (c.630A>C) is ultra-rare (popmax 0.0147%, nfe) (gnomAD).

PITX3 p.Pro210=

c.630A>C · VCV3358566

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, nfe)

Conditions

PITX3-related disorder

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -2.9	GERP -3.7
Overall
CADD	7.304	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0147% European (non-Finnish) · 168/1,146,268 alleles

Filtering AF 0.0128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.0114% 177/1,547,986 alleles · ultra-rare exomes 165/1,396,558 · genomes 12/151,428 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0147%	6,823
Remaining individualsnot grpmax-eligible	0.0133%	7,496
African / African-American	0.00138%	72,506

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: PITX3
Protein: p.Pro210=
Coding: c.630A>C
MANE Select: NM_005029
Type: single nucleotide variant
Location: chr10:102230793 (GRCh38)

Full PITX3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PITX3-related disorder

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/pitx3-p-pro210 (accessed [today's date]).

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