Is ZNF142 p.Gly1526Val (c.4577G>T) pathogenic?

ZNF142 p.Gly1526Val (c.4577G>T) is classified Uncertain significance in ZNF142 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-16). AlphaMissense: likely benign (0.1208); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with ZNF142 p.Gly1526Val (c.4577G>T)?

ZNF142 p.Gly1526Val (c.4577G>T) is associated with Inborn genetic diseases (ClinVar).

How common is ZNF142 p.Gly1526Val (c.4577G>T) in the general population?

ZNF142 p.Gly1526Val (c.4577G>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about ZNF142 p.Gly1526Val (c.4577G>T)?

AlphaMissense predicts likely benign (score 0.1208) — an in-silico prediction, not a clinical call.

ZNF142 p.Gly1526Val

c.4577G>T · VCV3985551

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1208 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1208	likely benign
REVEL	0.144	moderately benign-leaning
SaProt	LLR -7.37	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4	GERP 1.6, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 1,854 bp · p 0.8 · regional, not allelic
Overall
CADD	20.8	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 G1326V vs ClinVar G1526V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,866 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,611,112 alleles · very rare exomes 0/1,458,968 · genomes 2/152,144 · 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: ZNF142
Protein: p.Gly1526Val
Coding: c.4577G>T
MANE Select: NM_001379659
Type: single nucleotide variant
Location: chr2:218642539 (GRCh38)
Gene constraint: LOEUF 0.832 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.51
Residue 1326 UniProt numbering: a UniProt-annotated variant site (in nedishm)

Full ZNF142 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ZNF142 p.Ala1790Thr Uncertain significance ★★ ⚠ same condition
ZNF142 p.Ala720Pro Uncertain significance ★★ ⚠ same condition
ZNF142 p.Arg1023Trp Uncertain significance ★★ ⚠ same condition
ZNF142 p.Arg1079Cys Uncertain significance ★★ ⚠ same condition
ZNF142 p.Arg1253Cys Uncertain significance ★★ ⚠ same condition
ZNF142 p.Arg1412Gln Uncertain significance ★★ ⚠ same condition
ZNF142 p.Arg1447Gln Uncertain significance ★★ ⚠ same condition
ZNF142 p.Arg1469His 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/znf142-p-gly1526val (accessed [today's date]).

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