Is DZIP3 p.Ile923Val (c.2767A>G) pathogenic?

DZIP3 p.Ile923Val (c.2767A>G) is classified Uncertain significance in DZIP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-26). AlphaMissense: ambiguous (0.3943); Very rare (popmax 0.00224%, eas).

How common is DZIP3 p.Ile923Val (c.2767A>G) in the general population?

DZIP3 p.Ile923Val (c.2767A>G) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about DZIP3 p.Ile923Val (c.2767A>G)?

AlphaMissense predicts ambiguous (score 0.3943) — an in-silico prediction, not a clinical call.

DZIP3 p.Ile923Val

c.2767A>G · VCV3274273

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3943 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3943	ambiguous
REVEL	0.101	moderately benign-leaning
SaProt	LLR -5.34	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 83 kb · p 0.28 · regional, not allelic
Overall
CADD	24.8	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 0.00224% East Asian · 1/44,658 alleles

Overall 6.86e-05% 1/1,457,590 alleles · very rare

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: DZIP3
Protein: p.Ile923Val
Coding: c.2767A>G
MANE Select: NM_014648
Type: single nucleotide variant
Location: chr3:108675859 (GRCh38)
Gene constraint: LOEUF 0.781 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.63

Full DZIP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DZIP3 c.456+10A>G Benign ★★ same type
DZIP3 p.Asp6Gly Benign ★★ same type
DZIP3 p.Ala1018Ser Uncertain significance ★ ⚠ same type
DZIP3 p.Ala114Val Uncertain significance ★ ⚠ same type
DZIP3 p.Ala14Thr Uncertain significance ★ ⚠ same type
DZIP3 p.Ala714Thr Uncertain significance ★ ⚠ same type
DZIP3 p.Ala793Thr Uncertain significance ★ ⚠ same type
DZIP3 p.Ala854Thr 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/dzip3-p-ile923val (accessed [today's date]).

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