Is ZCCHC8 p.Pro482Arg (c.1445C>G) pathogenic?

ZCCHC8 p.Pro482Arg (c.1445C>G) is classified Uncertain significance in ZCCHC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-29). AlphaMissense: likely benign (0.094); Absent from gnomAD v4.1.

How common is ZCCHC8 p.Pro482Arg (c.1445C>G) in the general population?

ZCCHC8 p.Pro482Arg (c.1445C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ZCCHC8 p.Pro482Arg (c.1445C>G)?

AlphaMissense predicts likely benign (score 0.094) — an in-silico prediction, not a clinical call.

ZCCHC8 p.Pro482Arg

c.1445C>G · rs1957370518 · VCV2772799

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.094 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.094	likely benign
REVEL	0.248	benign-leaning
SaProt	LLR -8.23	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 4.7	GERP 0.47, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 27 kb · p 2.3e-06 · regional, not allelic
Overall
CADD	17.6	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: ZCCHC8
Protein: p.Pro482Arg
Coding: c.1445C>G
MANE Select: NM_017612
dbSNP: rs1957370518
Type: single nucleotide variant
Location: chr12:122474176 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.25 · 8 PDB
Residue 482: the 'disordered' region

Full ZCCHC8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ZCCHC8 p.Pro482= Benign/Likely benign ★★ same residue
ZCCHC8 p.Ala392Ser Uncertain significance ★★ ⚠ same type
ZCCHC8 p.Ala409Glu Uncertain significance ★★ ⚠ same type
ZCCHC8 p.Ala409Val Uncertain significance ★★ ⚠ same type
ZCCHC8 p.Ala442Val Uncertain significance ★★ ⚠ same type
ZCCHC8 p.Ala47Ser Uncertain significance ★★ ⚠ same type
ZCCHC8 p.Ala514Thr Uncertain significance ★★ ⚠ same type
ZCCHC8 p.Ala667Val Uncertain significance ★★ ⚠ same type

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/zcchc8-p-pro482arg (accessed [today's date]).

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