Is PRDM12 p.Ser71= (c.213C>T) pathogenic?

PRDM12 p.Ser71= (c.213C>T) is classified Likely benign in PRDM12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-11). Absent from gnomAD v4.1; Associated with congenital insensitivity to pain-hypohidrosis syndrome.

What condition is associated with PRDM12 p.Ser71= (c.213C>T)?

PRDM12 p.Ser71= (c.213C>T) is associated with congenital insensitivity to pain-hypohidrosis syndrome (ClinVar).

How common is PRDM12 p.Ser71= (c.213C>T) in the general population?

PRDM12 p.Ser71= (c.213C>T) is absent from gnomAD v4.1 (gnomAD).

PRDM12 p.Ser71=

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.213C>T · VCV4764858

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

congenital insensitivity to pain-hypohidrosis syndrome

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 0.71	GERP -0.28, phastCons 1
Overall
CADD	11.13	PHRED · no single calibrated threshold — expert panels disagree

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: PRDM12
Protein: p.Ser71=
Coding: c.213C>T
MANE Select: NM_021619
Type: single nucleotide variant
Location: chr9:130664866 (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.Ala332Val Uncertain significance ★★ ⚠ same condition
PRDM12 p.Arg147Cys Uncertain significance ★★ same condition
PRDM12 p.Arg147His Uncertain significance ★★ ⚠ same condition
PRDM12 p.Arg158Trp Uncertain significance ★★ ⚠ same condition
PRDM12 p.Asn134Ser Uncertain significance ★★ ⚠ same condition
PRDM12 p.Asn141Ser Uncertain significance ★★ ⚠ same condition
PRDM12 p.Asn207Ser Uncertain significance ★★ ⚠ same condition
PRDM12 p.Asn277Lys 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-ser71 (accessed [today's date]).

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