Is DZIP1L p.Ser406Pro (c.1216T>C) pathogenic?

DZIP1L p.Ser406Pro (c.1216T>C) is classified Uncertain significance in DZIP1L (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-25). AlphaMissense: likely benign (0.2748); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with DZIP1L p.Ser406Pro (c.1216T>C)?

DZIP1L p.Ser406Pro (c.1216T>C) is associated with Inborn genetic diseases (ClinVar).

How common is DZIP1L p.Ser406Pro (c.1216T>C) in the general population?

DZIP1L p.Ser406Pro (c.1216T>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about DZIP1L p.Ser406Pro (c.1216T>C)?

AlphaMissense predicts likely benign (score 0.2748) — an in-silico prediction, not a clinical call.

DZIP1L p.Ser406Pro

c.1216T>C · rs1943664711 · VCV2285709

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2748 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2748	likely benign
REVEL	0.201	benign-leaning
SaProt	LLR -11.28	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP 0.3, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 41 kb · p 0.44 · regional, not allelic
Overall
CADD	23.6	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 0.00133% African / African-American · 1/75,046 alleles

Overall 6.2e-05% 1/1,613,392 alleles · very rare exomes 1/1,461,028 · genomes 0/152,364 · joint denominator

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.Ser406Pro
Coding: c.1216T>C
MANE Select: NM_173543
dbSNP: rs1943664711
Type: single nucleotide variant
Location: chr3:138081752 (GRCh38)
Gene constraint: LOEUF 1.257 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.03
Residue 406: a UniProt-annotated variant site (in pkd5)

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-ser406pro (accessed [today's date]).

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