Is PITX3 p.Ser231= (c.693C>T) pathogenic?

PITX3 p.Ser231= (c.693C>T) is classified Likely benign in PITX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-18). Very rare (popmax 8.84e-05%, nfe).

How common is PITX3 p.Ser231= (c.693C>T) in the general population?

PITX3 p.Ser231= (c.693C>T) is very rare (popmax 8.84e-05%, nfe) (gnomAD).

PITX3 p.Ser231=

c.693C>T · VCV4752294

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.84e-05%, nfe)

⚠ 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 4.1	GERP -0.24, phastCons 1
Overall
CADD	13.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.84e-05% European (non-Finnish) · 1/1,131,354 alleles

Overall 6.62e-05% 1/1,510,022 alleles · very rare exomes 1/1,357,814 · genomes 0/152,208 · 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: PITX3
Protein: p.Ser231=
Coding: c.693C>T
MANE Select: NM_005029
Type: single nucleotide variant
Location: chr10:102230730 (GRCh38)

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

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-ser231 (accessed [today's date]).

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