Is DZIP1 p.Ala124Val (c.371C>T) pathogenic?

DZIP1 p.Ala124Val (c.371C>T) is classified Uncertain significance in DZIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-08). AlphaMissense: likely pathogenic (0.9504); Very rare (popmax 0.00237%, nfe).

How common is DZIP1 p.Ala124Val (c.371C>T) in the general population?

DZIP1 p.Ala124Val (c.371C>T) is very rare (popmax 0.00237%, nfe) (gnomAD).

What do computational predictors say about DZIP1 p.Ala124Val (c.371C>T)?

AlphaMissense predicts likely pathogenic (score 0.9504) — an in-silico prediction, not a clinical call.

DZIP1 p.Ala124Val

c.371C>T · rs754737561 · VCV2361183

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9504 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00237%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9504	likely pathogenic · top 6% in DZIP1
REVEL	0.339	indeterminate
SaProt	LLR -8.30	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 60 kb · p 0.38 · regional, not allelic
Overall
CADD	29.2	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 0.00237% European (non-Finnish) · 28/1,180,044 alleles

Filtering AF 0.00164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00198% 29/1,461,702 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00237%	42,144
African / African-American	0.00133%	75,074

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.Ala124Val
Coding: c.371C>T
MANE Select: NM_198968
dbSNP: rs754737561
Type: single nucleotide variant
Location: chr13:95641521 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.55
Residue 124: the 'mediates interaction with gli3 and localization to the cilium basal body' region; the 'mediates interaction with pcm1' region

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

Similar variants

DZIP1 p.His262Arg Uncertain significance ★★ ⚠ same type
DZIP1 p.Met664Leu Benign ★★ same type
DZIP1 p.Thr222= Benign ★★ same type
DZIP1 p.Ala211Ser Uncertain significance ★ ⚠ same type
DZIP1 p.Ala265Gly Uncertain significance ★ ⚠ same type
DZIP1 p.Ala32Val Uncertain significance ★ ⚠ same type
DZIP1 p.Ala380Gly Uncertain significance ★ ⚠ same type
DZIP1 p.Ala38Ser 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/dzip1-p-ala124val (accessed [today's date]).

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