Is ZNF469 p.Ser1663= (c.4989C>T) pathogenic?

ZNF469 p.Ser1663= (c.4989C>T) is classified Benign/Likely benign in ZNF469 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-24). Ultra-rare (popmax 0.044%, eas); Associated with Cardiovascular phenotype.

What condition is associated with ZNF469 p.Ser1663= (c.4989C>T)?

ZNF469 p.Ser1663= (c.4989C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is ZNF469 p.Ser1663= (c.4989C>T) in the general population?

ZNF469 p.Ser1663= (c.4989C>T) is ultra-rare (popmax 0.044%, eas) (gnomAD).

ZNF469 p.Ser1663=

c.4989C>T · rs369706261 · VCV1744009

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.044%, eas)

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 -2.3	GERP -2.6
Overall
CADD	0.16	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.044% East Asian · 18/40,928 alleles

Filtering AF 0.0284% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0234%

Overall 0.00155% 24/1,550,240 alleles · ultra-rare exomes 21/1,398,010 · genomes 3/152,230 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.044%	2,274
Remaining individualsnot grpmax-eligible	0.00666%	15,019
African / African-American	0.00137%	73,066
European (non-Finnish)	8.72e-05%	1,146,992

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.Ser1663=
Coding: c.4989C>T
MANE Select: NM_001367624
dbSNP: rs369706261
Type: single nucleotide variant
Location: chr16:88432459 (GRCh38)
Gene constraint: LOEUF 1.711 · pLI 0.26 (gnomAD)

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.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
ZNF469 p.Ala1329Thr 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-ser1663 (accessed [today's date]).

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