Is DZIP3 p.Arg185His (c.554G>A) pathogenic?

DZIP3 p.Arg185His (c.554G>A) is classified Uncertain significance in DZIP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-29). AlphaMissense: ambiguous (0.4361); Ultra-rare (popmax 0.0165%, mid).

How common is DZIP3 p.Arg185His (c.554G>A) in the general population?

DZIP3 p.Arg185His (c.554G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about DZIP3 p.Arg185His (c.554G>A)?

AlphaMissense predicts ambiguous (score 0.4361) — an in-silico prediction, not a clinical call.

DZIP3 p.Arg185His

c.554G>A · rs137935085 · VCV3086725

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4361 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4361	ambiguous
REVEL	0.095	moderately benign-leaning
SaProt	LLR -7.05	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 9.4	GERP 2.5, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 83 kb · p 0.28 · regional, not allelic
Overall
CADD	23.7	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 0.0165% Middle Eastern · 1/6,076 alleles

Filtering AF 0.00231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00304% 49/1,613,338 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,076
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,584
Admixed American	0.00334%	29,946
Remaining individualsnot grpmax-eligible	0.0032%	31,229
European (non-Finnish)	0.00314%	31,886
African / African-American	0.00267%	37,445
East Asian	0.00223%	44,848
South Asian	0.0022%	45,425
Finnishnot grpmax-eligible	0.00156%	64,038

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.Arg185His
Coding: c.554G>A
MANE Select: NM_014648
dbSNP: rs137935085
Type: single nucleotide variant
Location: chr3:108625942 (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-arg185his (accessed [today's date]).

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