Is PCNT p.Arg2865fs (c.8593_8594del) pathogenic?

PCNT p.Arg2865fs (c.85938594del) is classified Pathogenic in PCNT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-03). Very rare (popmax 0.00769%, sas); Associated with PCNT-related disorder.

What condition is associated with PCNT p.Arg2865fs (c.8593_8594del)?

PCNT p.Arg2865fs (c.8593_8594del) is associated with PCNT-related disorder, microcephalic osteodysplastic primordial dwarfism type II (ClinVar).

How common is PCNT p.Arg2865fs (c.8593_8594del) in the general population?

PCNT p.Arg2865fs (c.8593_8594del) is very rare (popmax 0.00769%, sas) (gnomAD).

PCNT p.Arg2865fs

c.8593_8594del · rs751242426 · VCV2632726

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Conditions

PCNT-related disorder

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 38 of 47
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.7	GERP 0.31, phastCons 0.006
Overall
CADD	27.2	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 0.00769% South Asian · 7/91,078 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.000991% 16/1,613,908 alleles · very rare exomes 11/1,461,600 · genomes 5/152,308 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	13,011
Admixed American	0.00666%	15,006
European (non-Finnish)	0.000424%	235,999

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.Arg2865fs
Coding: c.8593_8594del
MANE Select: NM_006031
dbSNP: rs751242426
Type: Microsatellite
Location: chr21:46432048 (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

PCNT-related disorder

Also linked: microcephalic osteodysplastic primordial dwarfism type II

Similar variants

PCNT p.Arg2865= Likely benign same residue
PCNT p.Arg388fs Pathogenic ★★ same condition
PCNT p.Leu1007fs Pathogenic ★★ same condition
PCNT p.Ser1142fs Pathogenic/Likely pathogenic ★★ same condition
PCNT p.Val557fs Pathogenic ★★ same condition
PCNT p.Ala2873fs Likely pathogenic ★ same condition
PCNT p.Arg1646fs Pathogenic ★ same condition
PCNT p.Cys64fs 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-arg2865fs (accessed [today's date]).

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