Is DZIP1 p.Lys16Arg (c.47A>G) pathogenic?

DZIP1 p.Lys16Arg (c.47A>G) is classified Uncertain significance in DZIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-24). AlphaMissense: likely benign (0.1006); Ultra-rare (popmax 0.0247%, amr).

How common is DZIP1 p.Lys16Arg (c.47A>G) in the general population?

DZIP1 p.Lys16Arg (c.47A>G) is ultra-rare (popmax 0.0247%, amr) (gnomAD).

What do computational predictors say about DZIP1 p.Lys16Arg (c.47A>G)?

AlphaMissense predicts likely benign (score 0.1006) — an in-silico prediction, not a clinical call.

DZIP1 p.Lys16Arg

c.47A>G · VCV4246021

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1006 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0247%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1006	likely benign
REVEL	0.087	moderately benign-leaning
SaProt	LLR -5.00	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 2.7	GERP 0.14, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 60 kb · p 0.38 · regional, not allelic
Overall
CADD	24.1	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 0.0247% Admixed American · 8/32,410 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00892%

Overall 0.000828% 12/1,448,760 alleles · ultra-rare exomes 9/1,297,724 · genomes 3/151,036 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0247%	4,051
Ashkenazi Jewishnot grpmax-eligible	0.00453%	22,070
Remaining individualsnot grpmax-eligible	0.0018%	55,472
African / African-American	0.00151%	66,240
South Asian	0.00147%	68,000

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.Lys16Arg
Coding: c.47A>G
MANE Select: NM_198968
Type: single nucleotide variant
Location: chr13:95641845 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.55
Residue 16: the 'mediates interaction with gli3 and localization to the cilium basal body' region; the 'mediates interaction with pcm1' 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-lys16arg (accessed [today's date]).

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