Is DZIP1 p.Ser24Arg (c.72C>A) pathogenic?

DZIP1 p.Ser24Arg (c.72C>A) is classified Uncertain significance in DZIP1 (ClinVar, Single submitter, 3 submitters; last evaluated 2022-06-08). AlphaMissense: likely benign (0.2277); Very rare (popmax 0.00828%, amr); Associated with spermatogenic failure 47.

What condition is associated with DZIP1 p.Ser24Arg (c.72C>A)?

DZIP1 p.Ser24Arg (c.72C>A) is associated with spermatogenic failure 47, mitral valve prolapse, myxomatous 3 (ClinVar).

How common is DZIP1 p.Ser24Arg (c.72C>A) in the general population?

DZIP1 p.Ser24Arg (c.72C>A) is very rare (popmax 0.00828%, amr) (gnomAD).

What do computational predictors say about DZIP1 p.Ser24Arg (c.72C>A)?

AlphaMissense predicts likely benign (score 0.2277) — an in-silico prediction, not a clinical call.

DZIP1 p.Ser24Arg

c.72C>A · rs1378714230 · VCV984961

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2277 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00828%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

spermatogenic failure 47

Computational evidence

Protein change
AlphaMissense	0.2277	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -6.35	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 1.1	GERP -1.5
Regional constraint	o/e 0.97	unconstrained · MANE · 60 kb · p 0.38 · regional, not allelic
Overall
CADD	15.3	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 0.00828% Admixed American · 3/36,226 alleles

Filtering AF 0.00315% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00282%

Overall 0.00361% 53/1,469,108 alleles · very rare exomes 50/1,317,682 · genomes 3/151,426 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00828%	12,075
Remaining individualsnot grpmax-eligible	0.00708%	14,131
European (non-Finnish)	0.00411%	24,339

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.Ser24Arg
Coding: c.72C>A
MANE Select: NM_198968
dbSNP: rs1378714230
Type: single nucleotide variant
Location: chr13:95641820 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.55
Residue 24: the 'mediates interaction with gli3 and localization to the cilium basal body' region; a UniProt-annotated variant site (in mvp3; decreased protein stability); the 'mediates interaction with pcm1' region

Full DZIP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spermatogenic failure 47 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: mitral valve prolapse, myxomatous 3

Similar variants

DZIP1 p.Ser24Asn Uncertain significance ★ ⚠ same residue
DZIP1 p.His262Arg Uncertain significance ★★ ⚠ same condition
DZIP1 p.Arg63Gln Pathogenic same condition
DZIP1 p.Tyr230Ter Pathogenic same condition
DZIP1 p.Ser369fs Likely pathogenic ★ same condition
DZIP1 p.Val750fs Likely pathogenic ★ same condition
DZIP1 p.Met664Leu Benign ★★ same type
DZIP1 p.Thr222= Benign ★★ 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-ser24arg (accessed [today's date]).

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