Is PCNT p.Asp659fs (c.1975dup) pathogenic?

PCNT p.Asp659fs (c.1975dup) is classified Pathogenic in PCNT (ClinVar, Single submitter, 1 submitter; last evaluated 2016-08-30). Very rare (popmax 0.000508%, nfe); Associated with microcephalic osteodysplastic primordial dwarfism type II.

What condition is associated with PCNT p.Asp659fs (c.1975dup)?

PCNT p.Asp659fs (c.1975dup) is associated with microcephalic osteodysplastic primordial dwarfism type II (ClinVar).

How common is PCNT p.Asp659fs (c.1975dup) in the general population?

PCNT p.Asp659fs (c.1975dup) is very rare (popmax 0.000508%, nfe) (gnomAD).

PCNT p.Asp659fs

c.1975dup · rs1555956600 · VCV436258

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000508%, 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.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 13 of 47
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -3.1	GERP -2.6

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000508% European (non-Finnish) · 6/1,180,026 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,614,156 alleles · very rare exomes 6/1,461,830 · genomes 0/152,326 · joint denominator

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.Asp659fs
Coding: c.1975dup
MANE Select: NM_006031
dbSNP: rs1555956600
Type: Duplication
Location: chr21:46357008 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)

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.Ala2957fs Pathogenic ★★ same condition
PCNT p.Glu998fs Pathogenic/Likely pathogenic ★★ same condition
PCNT p.His2484fs Pathogenic/Likely pathogenic ★★ same condition
PCNT p.Leu1200fs Pathogenic/Likely pathogenic ★★ same condition
PCNT p.Val2138fs Pathogenic/Likely pathogenic ★★ same condition
PCNT p.Val3179fs Pathogenic/Likely pathogenic ★★ same condition
PCNT p.Arg143_Gln155dup Uncertain significance ★★ same condition
PCNT c.8751+23dup Benign ★★ 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-asp659fs (accessed [today's date]).

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