Is PITX3 p.Pro157Ser (c.469C>T) pathogenic?

PITX3 p.Pro157Ser (c.469C>T) is classified Uncertain significance in PITX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-20). AlphaMissense: likely benign (0.0833); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PITX3 p.Pro157Ser (c.469C>T)?

PITX3 p.Pro157Ser (c.469C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PITX3 p.Pro157Ser (c.469C>T) in the general population?

PITX3 p.Pro157Ser (c.469C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PITX3 p.Pro157Ser (c.469C>T)?

AlphaMissense predicts likely benign (score 0.0833) — an in-silico prediction, not a clinical call.

PITX3 p.Pro157Ser

c.469C>T · VCV3306752

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0833 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

⚠ 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
AlphaMissense	0.0833	likely benign
REVEL	0.379	indeterminate
SaProt	LLR -6.17	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6.4	GERP -3.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 525 bp · p 0.37 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PITX3
Protein: p.Pro157Ser
Coding: c.469C>T
MANE Select: NM_005029
Type: single nucleotide variant
Location: chr10:102230954 (GRCh38)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-pro157ser (accessed [today's date]).

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