Is DZIP3 p.Pro301Ala (c.901C>G) pathogenic?

DZIP3 p.Pro301Ala (c.901C>G) is classified Uncertain significance in DZIP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: likely benign (0.119); Ultra-rare (popmax 0.0101%, amr).

How common is DZIP3 p.Pro301Ala (c.901C>G) in the general population?

DZIP3 p.Pro301Ala (c.901C>G) is ultra-rare (popmax 0.0101%, amr) (gnomAD).

What do computational predictors say about DZIP3 p.Pro301Ala (c.901C>G)?

AlphaMissense predicts likely benign (score 0.119) — an in-silico prediction, not a clinical call.

DZIP3 p.Pro301Ala

c.901C>G · rs764009233 · VCV2248575

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.119 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0101%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.119	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -8.57	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 3.8	GERP 2.4, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 83 kb · p 0.28 · regional, not allelic
Overall
CADD	21.9	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 0.0101% Admixed American · 6/59,566 alleles

Filtering AF 0.00431% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00297%

Overall 0.000499% 8/1,602,060 alleles · ultra-rare exomes 8/1,449,940 · genomes 0/152,120 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0101%	9,928
Remaining individualsnot grpmax-eligible	0.00161%	61,990
South Asian	0.00111%	90,318

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.Pro301Ala
Coding: c.901C>G
MANE Select: NM_014648
dbSNP: rs764009233
Type: single nucleotide variant
Location: chr3:108634955 (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-pro301ala (accessed [today's date]).

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