Is DMXL2 p.Pro336= (c.1008C>G) pathogenic?

DMXL2 p.Pro336= (c.1008C>G) is classified Likely benign in DMXL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-01). Very rare (popmax 0.000339%, nfe).

How common is DMXL2 p.Pro336= (c.1008C>G) in the general population?

DMXL2 p.Pro336= (c.1008C>G) is very rare (popmax 0.000339%, nfe) (gnomAD).

DMXL2 p.Pro336=

c.1008C>G · VCV4875345

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.47	GERP -4, phastCons 0.81
Overall
CADD	1.315	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,756 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,461,520 alleles · very rare

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: DMXL2
Protein: p.Pro336=
Coding: c.1008C>G
MANE Select: NM_001378457
Type: single nucleotide variant
Location: chr15:51542430 (GRCh38)
Gene constraint: LOEUF 0.36 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)

Full DMXL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DMXL2 c.1618-10T>A Uncertain significance ★★ same type
DMXL2 c.213+4A>T Uncertain significance ★★ same type
DMXL2 c.2314+6T>G Uncertain significance ★★ same type
DMXL2 p.Ala1212Val Uncertain significance ★★ ⚠ same type
DMXL2 p.Ala1663Thr Uncertain significance ★★ ⚠ same type
DMXL2 p.Ala1712Gly Uncertain significance ★★ ⚠ same type
DMXL2 p.Ala2003Thr Uncertain significance ★★ ⚠ same type
DMXL2 p.Ala2014Pro 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/dmxl2-p-pro336 (accessed [today's date]).

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