Is DZIP1L p.Pro608= (c.1824C>T) pathogenic?

DZIP1L p.Pro608= (c.1824C>T) is classified Likely benign in DZIP1L (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). Ultra-rare (popmax 0.0225%, mid); Associated with Inborn genetic diseases.

What condition is associated with DZIP1L p.Pro608= (c.1824C>T)?

DZIP1L p.Pro608= (c.1824C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DZIP1L p.Pro608= (c.1824C>T) in the general population?

DZIP1L p.Pro608= (c.1824C>T) is ultra-rare (popmax 0.0225%, mid) (gnomAD).

DZIP1L p.Pro608=

c.1824C>T · VCV4246055

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0225%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.9	GERP -3.4
Overall
CADD	0.129	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0225% Middle Eastern · 1/4,446 alleles

Filtering AF 0.00348% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00239%

Overall 0.00266% 40/1,504,158 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0225%	4,446
South Asian	0.00803%	12,450
African / African-American	0.00421%	23,757
Ashkenazi Jewishnot grpmax-eligible	0.00415%	24,092
Remaining individualsnot grpmax-eligible	0.00347%	28,848
European (non-Finnish)	0.0024%	41,596

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: DZIP1L
Protein: p.Pro608=
Coding: c.1824C>T
MANE Select: NM_173543
Type: single nucleotide variant
Location: chr3:138068159 (GRCh38)
Gene constraint: LOEUF 1.257 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.03
Residue 608: a UniProt-annotated variant site (in pkd5); the 'disordered' region

Full DZIP1L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DZIP1L p.Ala190Val Uncertain significance ★★ ⚠ same condition
DZIP1L p.Arg124Cys Uncertain significance ★★ ⚠ same condition
DZIP1L p.Arg131Cys Uncertain significance ★★ ⚠ same condition
DZIP1L p.Arg233Gln Uncertain significance ★★ ⚠ same condition
DZIP1L p.Arg48Trp Uncertain significance ★★ ⚠ same condition
DZIP1L p.Arg500Gln Uncertain significance ★★ ⚠ same condition
DZIP1L p.Arg500Trp Uncertain significance ★★ ⚠ same condition
DZIP1L p.Arg574Cys Uncertain significance ★★ ⚠ same condition

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/dzip1l-p-pro608 (accessed [today's date]).

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