Is DZIP1 p.Arg757His (c.2270G>A) pathogenic?

DZIP1 p.Arg757His (c.2270G>A) is classified Likely benign in DZIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-18). AlphaMissense: likely benign (0.0603); Ultra-rare (popmax 0.0729%, sas).

How common is DZIP1 p.Arg757His (c.2270G>A) in the general population?

DZIP1 p.Arg757His (c.2270G>A) is ultra-rare (popmax 0.0729%, sas) (gnomAD).

What do computational predictors say about DZIP1 p.Arg757His (c.2270G>A)?

AlphaMissense predicts likely benign (score 0.0603) — an in-silico prediction, not a clinical call.

DZIP1 p.Arg757His

c.2270G>A · rs548987690 · VCV2513090

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0603 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0729%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0603	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -6.64	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 0.94	GERP -2.6, phastCons 0.9
Regional constraint	o/e 0.97	unconstrained · MANE · 60 kb · p 0.38 · regional, not allelic
Overall
CADD	1.175	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 0.0729% South Asian · 66/90,502 alleles

Filtering AF 0.0587% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0536%

Overall 0.00639% 103/1,611,128 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0729%	1,371
Remaining individualsnot grpmax-eligible	0.0144%	6,927
African / African-American	0.00401%	24,909
European (non-Finnish)	0.00212%	47,158

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.Arg757His
Coding: c.2270G>A
MANE Select: NM_198968
dbSNP: rs548987690
Type: single nucleotide variant
Location: chr13:95586085 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.55
Residue 757: a UniProt-annotated variant site (in spgf47; decreased protein abundance; changed ciliary basal body organization; loss of sperm flagellum assembly); the 'disordered' region

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

Similar variants

DZIP1 p.Arg757Leu 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-arg757his (accessed [today's date]).

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