Is DZIP1 p.Arg63Gln (c.188G>A) pathogenic?

DZIP1 p.Arg63Gln (c.188G>A) is classified Pathogenic in DZIP1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-11-17). AlphaMissense: likely pathogenic (0.9753); Very rare (popmax 0.00223%, eas); Associated with spermatogenic failure 47.

What condition is associated with DZIP1 p.Arg63Gln (c.188G>A)?

DZIP1 p.Arg63Gln (c.188G>A) is associated with spermatogenic failure 47 (ClinVar).

How common is DZIP1 p.Arg63Gln (c.188G>A) in the general population?

DZIP1 p.Arg63Gln (c.188G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about DZIP1 p.Arg63Gln (c.188G>A)?

AlphaMissense predicts likely pathogenic (score 0.9753) — an in-silico prediction, not a clinical call.

DZIP1 p.Arg63Gln

c.188G>A · rs1878524886 · VCV984963

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9753 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

spermatogenic failure 47

Computational evidence

Protein change
AlphaMissense	0.9753	likely pathogenic ✓ concordant with ClinVar · top 4% in DZIP1
REVEL	0.408	indeterminate
SaProt	LLR -13.60	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 60 kb · p 0.38 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,872 alleles

Overall 0.000138% 2/1,450,236 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,872
European (non-Finnish)	8.48e-05%	1,179,407

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: DZIP1
Protein: p.Arg63Gln
Coding: c.188G>A
MANE Select: NM_198968
dbSNP: rs1878524886
Type: single nucleotide variant
Location: chr13:95641704 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.55
Residue 63: the 'mediates interaction with gli3 and localization to the cilium basal body' region; a UniProt-annotated variant site (in spgf47; decreased protein abundance; loss of sperm flagellum assembly); the 'mediates interaction with pcm1' region

Full DZIP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spermatogenic failure 47 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DZIP1 p.His262Arg Uncertain significance ★★ ⚠ same condition
DZIP1 p.Ser24Arg Uncertain significance ★ ⚠ same condition
DZIP1 p.Tyr230Ter Pathogenic same condition
DZIP1 p.Ser369fs Likely pathogenic ★ same condition
DZIP1 p.Val750fs Likely pathogenic ★ same condition
DZIP1 p.Met664Leu Benign ★★ same type
DZIP1 p.Thr222= Benign ★★ same type
DZIP1 p.Ala124Val 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/dzip1-p-arg63gln (accessed [today's date]).

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