Is ZNF469 p.Pro3003= (c.9009G>A) pathogenic?

ZNF469 p.Pro3003= (c.9009G>A) is classified Likely benign in ZNF469 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-09). Ultra-rare (popmax 0.0499%, mid); Associated with Cardiovascular phenotype.

What condition is associated with ZNF469 p.Pro3003= (c.9009G>A)?

ZNF469 p.Pro3003= (c.9009G>A) is associated with Cardiovascular phenotype (ClinVar).

How common is ZNF469 p.Pro3003= (c.9009G>A) in the general population?

ZNF469 p.Pro3003= (c.9009G>A) is ultra-rare (popmax 0.0499%, mid) (gnomAD).

ZNF469 p.Pro3003=

c.9009G>A · rs762354725 · VCV1183055

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0499%, mid)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.96	GERP -0.12, phastCons 0.001
Overall
CADD	4.509	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0499% Middle Eastern · 3/6,010 alleles

Filtering AF 0.0135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00724%

Overall 0.00239% 37/1,546,760 alleles · ultra-rare exomes 27/1,394,550 · genomes 10/152,210 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0499%	2,003
African / African-American	0.011%	9,132
Admixed American	0.00392%	25,495
South Asian	0.00238%	42,029
European (non-Finnish)	0.00183%	54,617
Remaining individualsnot grpmax-eligible	0.00167%	60,048

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: ZNF469
Protein: p.Pro3003=
Coding: c.9009G>A
MANE Select: NM_001367624
dbSNP: rs762354725
Type: single nucleotide variant
Location: chr16:88436479 (GRCh38)
Gene constraint: LOEUF 1.711 · pLI 0.26 (gnomAD)
Residue 3003: the 'disordered' region

Full ZNF469 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ZNF469 p.Pro3003Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
ZNF469 p.Pro3003Gln Likely benign ★ same residue
ZNF469 p.Gln2149Ter Pathogenic ★★ same condition
ZNF469 p.Glu176Ter Pathogenic ★★ same condition
ZNF469 p.Ala1001Asp Uncertain significance ★★ ⚠ same condition
ZNF469 p.Ala1001Val Uncertain significance ★★ ⚠ same condition
ZNF469 p.Ala1006Thr Uncertain significance ★★ ⚠ same condition
ZNF469 p.Ala1095Thr Uncertain significance ★★ ⚠ same condition

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/znf469-p-pro3003 (accessed [today's date]).

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