Is ZNF462 p.Ala487Val (c.1460C>T) pathogenic?

ZNF462 p.Ala487Val (c.1460C>T) is classified Uncertain significance in ZNF462 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-03). AlphaMissense: likely benign (0.2931); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ZNF462 p.Ala487Val (c.1460C>T)?

ZNF462 p.Ala487Val (c.1460C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ZNF462 p.Ala487Val (c.1460C>T) in the general population?

ZNF462 p.Ala487Val (c.1460C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ZNF462 p.Ala487Val (c.1460C>T)?

AlphaMissense predicts likely benign (score 0.2931) — an in-silico prediction, not a clinical call.

ZNF462 p.Ala487Val

c.1460C>T · rs1830147574 · VCV2542919

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2931 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2931	likely benign
REVEL	0.115	moderately benign-leaning
SaProt	LLR -6.06	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 3.3	GERP 1.8, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 1,132 bp · p 0.00095 · regional, not allelic
Overall
CADD	21.2	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ZNF462
Protein: p.Ala487Val
Coding: c.1460C>T
MANE Select: NM_021224
dbSNP: rs1830147574
Type: single nucleotide variant
Location: chr9:106925372 (GRCh38)
Gene constraint: LOEUF 0.082 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 50.74 · 1 PDB
Residue 487: a UniProt-annotated variant site (in wska)

Full ZNF462 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

ZNF462 p.Arg1537Ter Pathogenic/Likely pathogenic ★★ same condition
ZNF462 p.Arg257Cys Uncertain significance ★★ ⚠ same condition
ZNF462 p.Glu899Lys Uncertain significance ★★ ⚠ same condition
ZNF462 p.His2127Gln Uncertain significance ★★ ⚠ same condition
ZNF462 p.Leu212Pro Uncertain significance ★★ ⚠ same condition
ZNF462 p.Lys271Arg Uncertain significance ★★ ⚠ same condition
ZNF462 p.Pro1426Thr Uncertain significance ★★ ⚠ same condition
ZNF462 p.Thr1013Ile 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/znf462-p-ala487val (accessed [today's date]).

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