Is DZIP1 p.His262Arg (c.785A>G) pathogenic?

DZIP1 p.His262Arg (c.785A>G) is classified Uncertain significance in DZIP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-26). AlphaMissense: likely benign (0.1121); Ultra-rare (popmax 0.0636%, nfe); Associated with spermatogenic failure 47.

What condition is associated with DZIP1 p.His262Arg (c.785A>G)?

DZIP1 p.His262Arg (c.785A>G) is associated with spermatogenic failure 47 (ClinVar).

How common is DZIP1 p.His262Arg (c.785A>G) in the general population?

DZIP1 p.His262Arg (c.785A>G) is ultra-rare (popmax 0.0636%, nfe) (gnomAD).

What do computational predictors say about DZIP1 p.His262Arg (c.785A>G)?

AlphaMissense predicts likely benign (score 0.1121) — an in-silico prediction, not a clinical call.

DZIP1 p.His262Arg

c.785A>G · VCV3779302

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1121 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0636%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

spermatogenic failure 47

Computational evidence

Protein change
AlphaMissense	0.1121	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -5.18	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 2.9	GERP 0.27, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 60 kb · p 0.38 · regional, not allelic
Overall
CADD	17.29	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

Grpmax group 0.0636% European (non-Finnish) · 750/1,179,620 alleles

Filtering AF 0.0597% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0582%

Overall 0.0479% 772/1,612,828 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0636%	1,573
Remaining individualsnot grpmax-eligible	0.0272%	3,673
African / African-American	0.00667%	14,998

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.His262Arg
Coding: c.785A>G
MANE Select: NM_198968
Type: single nucleotide variant
Location: chr13:95630014 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.55
Residue 262: the 'mediates interaction with gli3 and localization to the cilium basal body' region; a UniProt-annotated variant site (in spgf47; decreased protein abundance; changed ciliary basal body organization; loss of sperm flagellum assembly); the 'required for interaction with daz1' 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.Ser24Arg Uncertain significance ★ ⚠ same condition
DZIP1 p.Arg63Gln Pathogenic 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-his262arg (accessed [today's date]).

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