Is DZIP1L p.Pro762Ser (c.2284C>T) pathogenic?

DZIP1L p.Pro762Ser (c.2284C>T) is classified Benign/Likely benign in DZIP1L (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-17). AlphaMissense: likely benign (0.0775); Rare (popmax 0.456%, sas).

How common is DZIP1L p.Pro762Ser (c.2284C>T) in the general population?

DZIP1L p.Pro762Ser (c.2284C>T) is rare (popmax 0.456%, sas) (gnomAD).

What do computational predictors say about DZIP1L p.Pro762Ser (c.2284C>T)?

AlphaMissense predicts likely benign (score 0.0775) — an in-silico prediction, not a clinical call.

DZIP1L p.Pro762Ser

c.2284C>T · rs142617141 · VCV722788

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0775 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.456%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0775	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -6.27	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	GERP -0.89, phastCons 0.58
Regional constraint	o/e 0.98	unconstrained · MANE · 41 kb · p 0.44 · regional, not allelic
Overall
CADD	6.158	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 0.456% South Asian · 415/91,074 alleles

Filtering AF 0.419% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.405%

Overall 0.0649% 1,047/1,614,080 alleles · rare exomes 956/1,461,738 · genomes 91/152,342 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.32%	76
South Asiangrpmax	0.456%	219
Middle Eastern	0.402%	249
Remaining individualsnot grpmax-eligible	0.114%	880
Ashkenazi Jewishnot grpmax-eligible	0.0946%	1,057
Admixed American	0.0533%	1,876
European (non-Finnish)	0.039%	2,565
East Asian	0.00446%	22,440
African / African-American	0.00266%	37,530
Finnishnot grpmax-eligible	0.00156%	64,030

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DZIP1L
Protein: p.Pro762Ser
Coding: c.2284C>T
MANE Select: NM_173543
dbSNP: rs142617141
Type: single nucleotide variant
Location: chr3:138062836 (GRCh38)
Gene constraint: LOEUF 1.257 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.03
Residue 762: a UniProt-annotated variant site (in pkd5); the 'disordered' region

Full DZIP1L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DZIP1L p.Glu358Ter Pathogenic/Likely pathogenic ★★ same type
DZIP1L p.Ala190Val Uncertain significance ★★ ⚠ same type
DZIP1L p.Arg124Cys Uncertain significance ★★ ⚠ same type
DZIP1L p.Arg131Cys Uncertain significance ★★ ⚠ same type
DZIP1L p.Arg233Gln Uncertain significance ★★ ⚠ same type
DZIP1L p.Arg37His Uncertain significance ★★ ⚠ same type
DZIP1L p.Arg48Trp Uncertain significance ★★ ⚠ same type
DZIP1L p.Arg500Gln 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/dzip1l-p-pro762ser (accessed [today's date]).

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