Is DZIP1 p.Arg563His (c.1688G>A) pathogenic?

DZIP1 p.Arg563His (c.1688G>A) is classified Likely benign in DZIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-21). AlphaMissense: likely benign (0.0788); Very rare (popmax 0.00553%, nfe).

How common is DZIP1 p.Arg563His (c.1688G>A) in the general population?

DZIP1 p.Arg563His (c.1688G>A) is very rare (popmax 0.00553%, nfe) (gnomAD).

What do computational predictors say about DZIP1 p.Arg563His (c.1688G>A)?

AlphaMissense predicts likely benign (score 0.0788) — an in-silico prediction, not a clinical call.

DZIP1 p.Arg563His

c.1688G>A · rs751711382 · VCV3086679

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0788 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00553%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0788	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -7.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.86	GERP -1.6, phastCons 0.34
Regional constraint	o/e 0.97	unconstrained · MANE · 60 kb · p 0.38 · regional, not allelic
Overall
CADD	9.444	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 0.00553% European (non-Finnish) · 65/1,175,850 alleles

Filtering AF 0.00444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00405%

Overall 0.00437% 70/1,600,468 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00553%	18,090
South Asian	0.00341%	29,284
Admixed American	0.00177%	56,602
Remaining individualsnot grpmax-eligible	0.00161%	61,952

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.Arg563His
Coding: c.1688G>A
MANE Select: NM_198968
dbSNP: rs751711382
Type: single nucleotide variant
Location: chr13:95590434 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.55
Residue 563: a UniProt-annotated variant site (in spgf47; decreased protein abundance; changed ciliary basal body organization; loss of sperm flagellum assembly); the 'mediates interaction with gdi2 and rab8a' region

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

Similar variants

DZIP1 p.Arg563Leu Uncertain significance ★ ⚠ same residue
DZIP1 p.His262Arg Uncertain significance ★★ ⚠ same type
DZIP1 p.Met664Leu Benign ★★ same type
DZIP1 p.Thr222= Benign ★★ same type
DZIP1 p.Ala124Val Uncertain significance ★ ⚠ same type
DZIP1 p.Ala211Ser Uncertain significance ★ ⚠ same type
DZIP1 p.Ala265Gly Uncertain significance ★ ⚠ same type
DZIP1 p.Ala32Val 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-arg563his (accessed [today's date]).

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