Is DIXDC1 p.Ser522Arg (c.1566C>A) pathogenic?

DIXDC1 p.Ser522Arg (c.1566C>A) is classified Uncertain significance in DIXDC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-28). AlphaMissense: likely pathogenic (0.9607); Absent from gnomAD v4.1.

How common is DIXDC1 p.Ser522Arg (c.1566C>A) in the general population?

DIXDC1 p.Ser522Arg (c.1566C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DIXDC1 p.Ser522Arg (c.1566C>A)?

AlphaMissense predicts likely pathogenic (score 0.9607) — an in-silico prediction, not a clinical call.

DIXDC1 p.Ser522Arg

c.1566C>A · VCV4011922

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9607 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,554)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9607	likely pathogenic · top 5% in DIXDC1
REVEL	0.234	benign-leaning
SaProt	LLR -7.06	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 1.6, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 50 kb · p 0.0089 · regional, not allelic
Overall
CADD	24.8	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

No allele count reported in gnomAD v4.1 (AN 1,613,554). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DIXDC1
Protein: p.Ser522Arg
Coding: c.1566C>A
MANE Select: NM_001037954
Type: single nucleotide variant
Location: chr11:111995441 (GRCh38)
Gene constraint: LOEUF 0.783 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.52 · 1 PDB

Full DIXDC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DIXDC1 p.Asn19Asp Benign ★★ same type
DIXDC1 p.Asp608= Benign ★★ same type
DIXDC1 p.Ala156Pro Uncertain significance ★ ⚠ same type
DIXDC1 p.Ala25Pro Uncertain significance ★ ⚠ same type
DIXDC1 p.Ala39Val Uncertain significance ★ ⚠ same type
DIXDC1 p.Arg138Gln Uncertain significance ★ ⚠ same type
DIXDC1 p.Arg199Gln Uncertain significance ★ ⚠ same type
DIXDC1 p.Arg199Trp 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/dixdc1-p-ser522arg (accessed [today's date]).

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