Is PCNT p.Ser3093= (c.9279G>A) pathogenic?

PCNT p.Ser3093= (c.9279G>A) is classified Benign/Likely benign in PCNT (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-02-16). Rare (popmax 0.825%, eas); Associated with microcephalic osteodysplastic primordial dwarfism type II.

What condition is associated with PCNT p.Ser3093= (c.9279G>A)?

PCNT p.Ser3093= (c.9279G>A) is associated with microcephalic osteodysplastic primordial dwarfism type II (ClinVar).

How common is PCNT p.Ser3093= (c.9279G>A) in the general population?

PCNT p.Ser3093= (c.9279G>A) is rare (popmax 0.825%, eas) (gnomAD).

PCNT p.Ser3093=

c.9279G>A · rs199596313 · VCV899003

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.825%, eas)

Conditions

microcephalic osteodysplastic primordial dwarfism type II

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.006	strongly benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3.8	GERP -3.9
Overall
CADD	0.73	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.825% East Asian · 370/44,874 alleles

Filtering AF 0.755% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.728%

Overall 0.0255% 411/1,614,038 alleles · rare exomes 398/1,461,762 · genomes 13/152,276 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.825%	121
European (non-Finnish)	0.00322%	31,053
Remaining individualsnot grpmax-eligible	0.0032%	31,251
Admixed American	0.00167%	60,014

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.Ser3093=
Coding: c.9279G>A
MANE Select: NM_006031
dbSNP: rs199596313
Type: single nucleotide variant
Location: chr21:46440088 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)
Residue 3093: the 'disordered' region; the 'interaction with nek2' 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 p.Ser3093Leu Uncertain significance ★★ ⚠ same residue
PCNT p.Ser3093Trp Uncertain significance ★★ ⚠ same residue
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

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-ser3093 (accessed [today's date]).

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