Is DZIP1 p.Ser140Leu (c.419C>T) pathogenic?

DZIP1 p.Ser140Leu (c.419C>T) is classified Uncertain significance in DZIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: likely benign (0.1206); Very rare (popmax 0.00534%, afr).

How common is DZIP1 p.Ser140Leu (c.419C>T) in the general population?

DZIP1 p.Ser140Leu (c.419C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about DZIP1 p.Ser140Leu (c.419C>T)?

AlphaMissense predicts likely benign (score 0.1206) — an in-silico prediction, not a clinical call.

DZIP1 p.Ser140Leu

c.419C>T · rs151232719 · VCV2465653

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1206 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1206	likely benign
REVEL	0.123	moderately benign-leaning
SaProt	LLR -9.41	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 60 kb · p 0.38 · regional, not allelic
Overall
CADD	25.9	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 0.00534% African / African-American · 4/74,920 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000372% 6/1,613,972 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,730
Admixed American	0.00167%	60,008
European (non-Finnish)	8.47e-05%	1,180,027

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.Ser140Leu
Coding: c.419C>T
MANE Select: NM_198968
dbSNP: rs151232719
Type: single nucleotide variant
Location: chr13:95641473 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.55
Residue 140: 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.Ala124Val Uncertain significance ★ ⚠ 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

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-ser140leu (accessed [today's date]).

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