Is DZANK1 p.Ala331Asp (c.992C>A) pathogenic?

DZANK1 p.Ala331Asp (c.992C>A) is classified Uncertain significance in DZANK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: likely benign (0.1259); Absent from gnomAD v4.1.

How common is DZANK1 p.Ala331Asp (c.992C>A) in the general population?

DZANK1 p.Ala331Asp (c.992C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DZANK1 p.Ala331Asp (c.992C>A)?

AlphaMissense predicts likely benign (score 0.1259) — an in-silico prediction, not a clinical call.

DZANK1 p.Ala331Asp

c.992C>A · rs2516900424 · VCV3086676

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1259 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1259	likely benign
REVEL	0.51	indeterminate
SaProt	LLR -7.46	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.77	GERP -2.4, phastCons 0.34
Overall
CADD	12.6	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A312D vs ClinVar A331D) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DZANK1
Protein: p.Ala331Asp
Coding: c.992C>A
MANE Select: NM_001367614
dbSNP: rs2516900424
Type: single nucleotide variant
Location: chr20:18427086 (GRCh38)
Gene constraint: LOEUF 1.264 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.80 · 1 PDB

Full DZANK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DZANK1 p.Ala497Asp Uncertain significance ★★ ⚠ same type
DZANK1 p.Ala185Pro Uncertain significance ★ ⚠ same type
DZANK1 p.Ala205Val Uncertain significance ★ ⚠ same type
DZANK1 p.Ala291Pro Uncertain significance ★ ⚠ same type
DZANK1 p.Ala301Thr Uncertain significance ★ ⚠ same type
DZANK1 p.Ala681Val Uncertain significance ★ ⚠ same type
DZANK1 p.Ala719Pro Uncertain significance ★ ⚠ same type
DZANK1 p.Ala742Ser 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/dzank1-p-ala331asp (accessed [today's date]).

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