Is PRDM12 p.Val44fs (c.131_138del) pathogenic?

PRDM12 p.Val44fs (c.131138del) is classified Pathogenic in PRDM12 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-07-08). Absent from gnomAD; Associated with congenital insensitivity to pain-hypohidrosis syndrome.

What condition is associated with PRDM12 p.Val44fs (c.131_138del)?

PRDM12 p.Val44fs (c.131_138del) is associated with congenital insensitivity to pain-hypohidrosis syndrome (ClinVar).

How common is PRDM12 p.Val44fs (c.131_138del) in the general population?

PRDM12 p.Val44fs (c.131_138del) is absent from gnomAD (gnomAD).

PRDM12 p.Val44fs

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.131_138del · rs2132586619 · VCV1323492

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 1 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.3	GERP 0.82, 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.Val44fs
Coding: c.131_138del
MANE Select: NM_021619
dbSNP: rs2132586619
Type: Deletion
Location: chr9:130664783 (GRCh38)
Gene constraint: LOEUF 1.153 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.81 · 1 PDB

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.Val44= Likely benign ★ same residue
PRDM12 p.Leu347del Uncertain significance ★ same condition
PRDM12 p.Ala353fs Likely benign ★ same condition
PRDM12 p.Ala332Val Uncertain significance ★★ ⚠ same condition
PRDM12 p.Ala339_Pro340insHisSerProAlaLeuProAla Uncertain significance ★★ same condition
PRDM12 p.Ala348_Ala349insThr Uncertain significance ★★ same condition
PRDM12 p.Ala353_Ala359del Uncertain significance ★★ same condition
PRDM12 p.Ala355_Ala359dup Uncertain significance ★★ 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-val44fs (accessed [today's date]).

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