Is PCNT p.Ser3284= (c.9852C>T) pathogenic?

PCNT p.Ser3284= (c.9852C>T) is classified Conflicting classifications of pathogenicity in PCNT (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-12-16). Ultra-rare (popmax 0.0403%, nfe); Associated with microcephalic osteodysplastic primordial dwarfism type II.

What condition is associated with PCNT p.Ser3284= (c.9852C>T)?

PCNT p.Ser3284= (c.9852C>T) is associated with microcephalic osteodysplastic primordial dwarfism type II (ClinVar).

How common is PCNT p.Ser3284= (c.9852C>T) in the general population?

PCNT p.Ser3284= (c.9852C>T) is ultra-rare (popmax 0.0403%, nfe) (gnomAD).

PCNT p.Ser3284=

c.9852C>T · rs142800774 · VCV436239

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0403%, nfe)

Conditions

microcephalic osteodysplastic primordial dwarfism type II

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.14
Overall
CADD	3.802	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0403% European (non-Finnish) · 475/1,179,522 alleles

Filtering AF 0.0372% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0361%

Overall 0.0298% 481/1,612,770 alleles · ultra-rare exomes 461/1,461,226 · genomes 20/151,544 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0403%	2,483
Remaining individualsnot grpmax-eligible	0.00801%	12,491
African / African-American	0.00134%	74,660

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.Ser3284=
Coding: c.9852C>T
MANE Select: NM_006031
dbSNP: rs142800774
Type: single nucleotide variant
Location: chr21:46444706 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)
Residue 3284: the 'disordered' region

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

Disease context

microcephalic osteodysplastic primordial dwarfism type II — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PCNT c.1032+1G>A Pathogenic/Likely pathogenic ★★ same condition
PCNT c.1680-1G>C Likely pathogenic ★★ same condition
PCNT c.5995-2A>C Likely pathogenic ★★ same condition
PCNT c.7024+1G>C Likely pathogenic ★★ same condition
PCNT c.7691-1G>A Likely pathogenic ★★ same condition
PCNT c.9624-2A>G Likely pathogenic ★★ same condition
PCNT p.Arg1730Ter Pathogenic/Likely pathogenic ★★ same condition
PCNT p.Arg1923Ter Pathogenic/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-ser3284 (accessed [today's date]).

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