Is DZIP3 p.Asp6Ala (c.17A>C) pathogenic?

DZIP3 p.Asp6Ala (c.17A>C) is classified Uncertain significance in DZIP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-06). AlphaMissense: likely benign (0.1019); Very rare (popmax 0.0011%, nfe).

How common is DZIP3 p.Asp6Ala (c.17A>C) in the general population?

DZIP3 p.Asp6Ala (c.17A>C) is very rare (popmax 0.0011%, nfe) (gnomAD).

What do computational predictors say about DZIP3 p.Asp6Ala (c.17A>C)?

AlphaMissense predicts likely benign (score 0.1019) — an in-silico prediction, not a clinical call.

DZIP3 p.Asp6Ala

c.17A>C · VCV4662745

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1019 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1019	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -6.17	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.44 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.8	GERP 2.3, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 83 kb · p 0.28 · regional, not allelic
Overall
CADD	22.3	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 0.0011% European (non-Finnish) · 13/1,179,684 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000806% 13/1,613,386 alleles · very rare exomes 13/1,461,104 · genomes 0/152,282 · 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: DZIP3
Protein: p.Asp6Ala
Coding: c.17A>C
MANE Select: NM_014648
Type: single nucleotide variant
Location: chr3:108605423 (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 p.Asp6Gly Benign ★★ same residue
DZIP3 c.456+10A>G 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-asp6ala (accessed [today's date]).

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