Is PRDM12 p.Pro194fs (c.578dup) pathogenic?

PRDM12 p.Pro194fs (c.578dup) is classified Pathogenic in PRDM12 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-30). Absent from gnomAD; Associated with congenital insensitivity to pain-hypohidrosis syndrome.

What condition is associated with PRDM12 p.Pro194fs (c.578dup)?

PRDM12 p.Pro194fs (c.578dup) is associated with congenital insensitivity to pain-hypohidrosis syndrome (ClinVar).

How common is PRDM12 p.Pro194fs (c.578dup) in the general population?

PRDM12 p.Pro194fs (c.578dup) is absent from gnomAD (gnomAD).

PRDM12 p.Pro194fs

Q: How is Hereditary sensory and autonomic neuropathy type 8 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.578dup · rs2490743581 · VCV2706647

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

congenital insensitivity to pain-hypohidrosis syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 2.4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: PRDM12
Protein: p.Pro194fs
Coding: c.578dup
MANE Select: NM_021619
dbSNP: rs2490743581
Type: Duplication
Location: chr9:130678533 (GRCh38)
Gene constraint: LOEUF 1.153 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.81 · 1 PDB
Residue 194: the set domain

Full PRDM12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital insensitivity to pain-hypohidrosis syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary sensory and autonomic neuropathy type 8 (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

PRDM12 p.Ala339_Pro340insHisSerProAlaLeuProAla Uncertain significance ★★ same condition
PRDM12 p.Ala329fs Uncertain significance ★ same condition
PRDM12 p.Gln331_Leu337dup Uncertain significance ★ same condition
PRDM12 p.His333_Ala339dup Uncertain significance ★ same condition
PRDM12 p.Pro345_Ala346dup Uncertain significance ★ same condition
PRDM12 p.Pro345_Ala348dup Uncertain significance ★ same condition
PRDM12 p.Ser256_Arg263dup Uncertain significance ★ same condition
PRDM12 c.682+19dup Benign ★ same condition

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/prdm12-p-pro194fs (accessed [today's date]).

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