Is DZIP1 p.Cys604Trp (c.1812T>G) pathogenic?

DZIP1 p.Cys604Trp (c.1812T>G) is classified Benign in DZIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-01). AlphaMissense: likely benign (0.1822); Low-frequency (popmax 1.15%, sas).

How common is DZIP1 p.Cys604Trp (c.1812T>G) in the general population?

DZIP1 p.Cys604Trp (c.1812T>G) is low-frequency (popmax 1.15%, sas) (gnomAD).

What do computational predictors say about DZIP1 p.Cys604Trp (c.1812T>G)?

AlphaMissense predicts likely benign (score 0.1822) — an in-silico prediction, not a clinical call.

DZIP1 p.Cys604Trp

c.1812T>G · rs34181737 · VCV3250514

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1822 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.15%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1822	likely benign
REVEL	0.165	moderately benign-leaning
SaProt	LLR -7.28	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 1	GERP -5, phastCons 0.97
Regional constraint	o/e 0.97	unconstrained · MANE · 60 kb · p 0.38 · regional, not allelic
Overall
CADD	19.7	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 1.15% South Asian · 1,049/90,946 alleles

Filtering AF 1.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.07%

Overall 0.769% 12,414/1,613,668 alleles · low-frequency

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.87%	35
South Asiangrpmax	1.15%	87
Remaining individualsnot grpmax-eligible	0.747%	134
European (non-Finnish)	0.729%	137
Middle Eastern	0.366%	274
Ashkenazi Jewishnot grpmax-eligible	0.331%	302
Admixed American	0.263%	380
East Asian	0.205%	488
African / African-American	0.12%	834
Amishnot grpmax-eligible	0.11%	912

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Cys604Trp
Coding: c.1812T>G
MANE Select: NM_198968
dbSNP: rs34181737
Type: single nucleotide variant
Location: chr13:95590310 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.55
Residue 604: 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.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
DZIP1 p.Ala380Gly 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-cys604trp (accessed [today's date]).

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