Is DQX1 p.Pro46Ser (c.136C>T) pathogenic?

DQX1 p.Pro46Ser (c.136C>T) is classified Uncertain significance in DQX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-01). AlphaMissense: ambiguous (0.3428); Absent from gnomAD v4.1.

How common is DQX1 p.Pro46Ser (c.136C>T) in the general population?

DQX1 p.Pro46Ser (c.136C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DQX1 p.Pro46Ser (c.136C>T)?

AlphaMissense predicts ambiguous (score 0.3428) — an in-silico prediction, not a clinical call.

DQX1 p.Pro46Ser

c.136C>T · VCV3273727

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3428 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.3428	ambiguous
REVEL	0.465	indeterminate
SaProt	LLR -11.71	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 7,280 bp · p 0.018 · regional, not allelic
Overall
CADD	25.0	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

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: DQX1
Protein: p.Pro46Ser
Coding: c.136C>T
MANE Select: NM_133637
Type: single nucleotide variant
Location: chr2:74525594 (GRCh38)
Gene constraint: LOEUF 0.971 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.42

Full DQX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DQX1 p.Ala116Thr Uncertain significance ★ ⚠ same type
DQX1 p.Ala248Thr Uncertain significance ★ ⚠ same type
DQX1 p.Ala251Thr Uncertain significance ★ ⚠ same type
DQX1 p.Ala310Asp Uncertain significance ★ ⚠ same type
DQX1 p.Ala327Val Uncertain significance ★ ⚠ same type
DQX1 p.Ala477Val Uncertain significance ★ ⚠ same type
DQX1 p.Ala555Thr Uncertain significance ★ ⚠ same type
DQX1 p.Ala707Gly 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/dqx1-p-pro46ser (accessed [today's date]).

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