Is PCNT p.Arg3236Ter (c.9706C>T) pathogenic?

PCNT p.Arg3236Ter (c.9706C>T) is classified Pathogenic/Likely pathogenic in PCNT (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-10-29). Ultra-rare (popmax 0.0167%, amr); Associated with PCNT-related disorder.

What condition is associated with PCNT p.Arg3236Ter (c.9706C>T)?

PCNT p.Arg3236Ter (c.9706C>T) is associated with PCNT-related disorder, microcephalic osteodysplastic primordial dwarfism type II (ClinVar).

How common is PCNT p.Arg3236Ter (c.9706C>T) in the general population?

PCNT p.Arg3236Ter (c.9706C>T) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

PCNT p.Arg3236Ter

c.9706C>T · rs757793925 · VCV444580

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Conditions

PCNT-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 45 of 47
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.15
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% Admixed American · 10/60,002 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00681%

Overall 0.00353% 57/1,613,610 alleles · ultra-rare exomes 51/1,461,436 · genomes 6/152,174 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	6,000
Remaining individualsnot grpmax-eligible	0.00801%	12,488
European (non-Finnish)	0.00322%	31,052
Finnishnot grpmax-eligible	0.00312%	32,017
South Asian	0.0022%	45,532

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: PCNT
Protein: p.Arg3236Ter
Coding: c.9706C>T
MANE Select: NM_006031
dbSNP: rs757793925
Type: single nucleotide variant
Location: chr21:46443815 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)
Residue 3236: the 'disordered' region; the 'interaction with nek2' region

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

Disease context

PCNT-related disorder

Also linked: microcephalic osteodysplastic primordial dwarfism type II

Similar variants

PCNT p.Arg3236Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
PCNT c.1032+1G>A Pathogenic/Likely pathogenic ★★ same condition
PCNT c.1680-1G>C Likely pathogenic ★★ same condition
PCNT c.3313-2A>C Likely pathogenic ★★ same condition
PCNT c.5995-2A>C Likely pathogenic ★★ same condition
PCNT c.7024+1G>A Likely pathogenic ★★ same condition
PCNT c.7024+1G>C Likely pathogenic ★★ same condition
PCNT c.7691-1G>A Likely pathogenic ★★ 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/pcnt-p-arg3236ter (accessed [today's date]).

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