Is ZNF469 p.Ser2425= (c.7275C>T) pathogenic?

ZNF469 p.Ser2425= (c.7275C>T) is classified Likely benign in ZNF469 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-02). Very rare (popmax 0.00411%, afr); Associated with Cardiovascular phenotype.

What condition is associated with ZNF469 p.Ser2425= (c.7275C>T)?

ZNF469 p.Ser2425= (c.7275C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is ZNF469 p.Ser2425= (c.7275C>T) in the general population?

ZNF469 p.Ser2425= (c.7275C>T) is very rare (popmax 0.00411%, afr) (gnomAD).

ZNF469 p.Ser2425=

c.7275C>T · rs1174434294 · VCV1757598

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00411%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.37	GERP -3.5
Overall
CADD	0.949	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00411% African / African-American · 3/73,054 alleles

Filtering AF 0.00109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000502%

Overall 0.000194% 3/1,550,296 alleles · very rare exomes 2/1,398,068 · genomes 1/152,228 · 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: ZNF469
Protein: p.Ser2425=
Coding: c.7275C>T
MANE Select: NM_001367624
dbSNP: rs1174434294
Type: single nucleotide variant
Location: chr16:88434745 (GRCh38)
Gene constraint: LOEUF 1.711 · pLI 0.26 (gnomAD)
Residue 2425: 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.Ser2425Asn Uncertain significance ★ ⚠ 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
ZNF469 p.Ala1251Thr 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-ser2425 (accessed [today's date]).

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