Is PITX3 p.Ile95= (c.285C>T) pathogenic?

PITX3 p.Ile95= (c.285C>T) is classified Benign in PITX3 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-02). Common (popmax 75.1%, afr) — too common for a highly-penetrant pathogenic allele; Associated with anterior segment dysgenesis 1.

What condition is associated with PITX3 p.Ile95= (c.285C>T)?

PITX3 p.Ile95= (c.285C>T) is associated with anterior segment dysgenesis 1, cataract 11 multiple types (ClinVar).

PITX3 p.Ile95=

Q: How common is PITX3 p.Ile95= (c.285C>T) in the general population?

PITX3 p.Ile95= (c.285C>T) is common (popmax 75.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.285C>T · rs2281983 · VCV196404

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 75.1%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

anterior segment dysgenesis 1

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 2.4	GERP -1.8, phastCons 1
Overall
CADD	13.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 75.1% African / African-American · 56,282/74,916 alleles

Filtering AF 74.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 74.4%

Overall 62.4% 1,003,836/1,608,126 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	75.1%	1
East Asian	73.7%	1
Remaining individualsnot grpmax-eligible	62.4%	2
European (non-Finnish)	62.4%	2
Finnishnot grpmax-eligible	61.5%	2
Admixed American	59.4%	2
Amishnot grpmax-eligible	59.1%	2
Ashkenazi Jewishnot grpmax-eligible	57.7%	2
Middle Eastern	55.2%	2
South Asian	51.2%	2

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.Ile95=
Coding: c.285C>T
MANE Select: NM_001377137 · reported on NM_005029
dbSNP: rs2281983
Type: single nucleotide variant
Location: chr10:102231624 (GRCh38)

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

Disease context

anterior segment dysgenesis 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cataract 11 multiple types

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-ile95 (accessed [today's date]).

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