Is ZNF423 p.Gly926Val (c.2777G>T) pathogenic?

ZNF423 p.Gly926Val (c.2777G>T) is classified Uncertain significance in ZNF423 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-07-30). AlphaMissense: likely benign (0.0843); No allele count reported in gnomAD v4.1 (AN 1,613,232); Associated with nephronophthisis 14.

What condition is associated with ZNF423 p.Gly926Val (c.2777G>T)?

ZNF423 p.Gly926Val (c.2777G>T) is associated with nephronophthisis 14 (ClinVar).

How common is ZNF423 p.Gly926Val (c.2777G>T) in the general population?

ZNF423 p.Gly926Val (c.2777G>T) is no allele count reported in gnomAD v4.1 (AN 1,613,232) (gnomAD).

How is Nephronophthisis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ZNF423 p.Gly926Val (c.2777G>T)?

AlphaMissense predicts likely benign (score 0.0843) — an in-silico prediction, not a clinical call.

ZNF423 p.Gly926Val

c.2777G>T · rs1972705896 · VCV1038485

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0843 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,232)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nephronophthisis 14

Computational evidence

Protein change
AlphaMissense	0.0843	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -7.12	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP -3.2, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 1,702 bp · p 2.3e-08 · regional, not allelic
Overall
CADD	19.98	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM G918V vs ClinVar G926V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,232). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ZNF423
Protein: p.Gly926Val
Coding: c.2777G>T
MANE Select: NM_001379286
dbSNP: rs1972705896
Type: single nucleotide variant
Location: chr16:49636399 (GRCh38)
Gene constraint: LOEUF 0.196 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.63 · 1 PDB

Full ZNF423 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

nephronophthisis 14 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Nephronophthisis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Finland)

Similar variants

ZNF423 c.40+33052G>A Uncertain significance ★★ same condition
ZNF423 p.Ala1075Thr Uncertain significance ★★ ⚠ same condition
ZNF423 p.Ala1101Thr Uncertain significance ★★ ⚠ same condition
ZNF423 p.Ala1108Thr Uncertain significance ★★ ⚠ same condition
ZNF423 p.Ala1291Val Uncertain significance ★★ ⚠ same condition
ZNF423 p.Ala19Val Uncertain significance ★★ ⚠ same condition
ZNF423 p.Ala25Gly Uncertain significance ★★ ⚠ same condition
ZNF423 p.Ala25Thr 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/znf423-p-gly926val (accessed [today's date]).

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