Is ZCCHC8 p.Arg79= (c.237A>G) pathogenic?

ZCCHC8 p.Arg79= (c.237A>G) is classified Likely benign in ZCCHC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-16). Absent from gnomAD v4.1.

How common is ZCCHC8 p.Arg79= (c.237A>G) in the general population?

ZCCHC8 p.Arg79= (c.237A>G) is absent from gnomAD v4.1 (gnomAD).

ZCCHC8 p.Arg79=

c.237A>G · rs2547220463 · VCV2127077

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.3	GERP 0.52, phastCons 1
Overall
CADD	11.97	PHRED · no single calibrated threshold — expert panels disagree

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.Arg79=
Coding: c.237A>G
MANE Select: NM_017612
dbSNP: rs2547220463
Type: single nucleotide variant
Location: chr12:122498832 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.25 · 8 PDB

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

Similar variants

ZCCHC8 p.Arg79Gln Uncertain significance ★ ⚠ 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-arg79 (accessed [today's date]).

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