Is PITX3 p.Pro191Ser (c.571C>T) pathogenic?

PITX3 p.Pro191Ser (c.571C>T) is classified Uncertain significance in PITX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-06-10). AlphaMissense: likely benign (0.0943); Very rare (popmax 0.00113%, sas).

How common is PITX3 p.Pro191Ser (c.571C>T) in the general population?

PITX3 p.Pro191Ser (c.571C>T) is very rare (popmax 0.00113%, sas) (gnomAD).

What do computational predictors say about PITX3 p.Pro191Ser (c.571C>T)?

AlphaMissense predicts likely benign (score 0.0943) — an in-silico prediction, not a clinical call.

PITX3 p.Pro191Ser

c.571C>T · VCV4909352

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0943 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00113%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

⚠ 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	0.0943	likely benign
REVEL	0.75	pathogenic-leaning
SaProt	LLR -6.00	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 525 bp · p 0.37 · regional, not allelic
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00113% South Asian · 1/88,700 alleles

Overall 6.27e-05% 1/1,595,976 alleles · very rare exomes 1/1,443,698 · genomes 0/152,278 · 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.Pro191Ser
Coding: c.571C>T
MANE Select: NM_005029
Type: single nucleotide variant
Location: chr10:102230852 (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-pro191ser (accessed [today's date]).

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