Is PCNT p.Cys2014fs (c.6038dup) pathogenic?

PCNT p.Cys2014fs (c.6038dup) is classified Pathogenic in PCNT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-29). Very rare (popmax 0.00267%, afr).

How common is PCNT p.Cys2014fs (c.6038dup) in the general population?

PCNT p.Cys2014fs (c.6038dup) is very rare (popmax 0.00267%, afr) (gnomAD).

PCNT p.Cys2014fs

c.6038dup · rs752986448 · VCV2847037

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

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 29 of 47
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.071	GERP -3
Overall
CADD	22.5	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 0.00267% African / African-American · 2/74,946 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,612,766 alleles · very rare exomes 0/1,460,502 · genomes 2/152,264 · 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.Cys2014fs
Coding: c.6038dup
MANE Select: NM_006031
dbSNP: rs752986448
Type: Duplication
Location: chr21:46412879 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)

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

Similar variants

PCNT p.Ala2957fs Pathogenic ★★ same type
PCNT p.Gln783fs Pathogenic ★★ same type
PCNT p.Glu998fs Pathogenic/Likely pathogenic ★★ same type
PCNT p.His2484fs Pathogenic/Likely pathogenic ★★ same type
PCNT p.Leu1200fs Pathogenic/Likely pathogenic ★★ same type
PCNT p.Val2138fs Pathogenic/Likely pathogenic ★★ same type
PCNT p.Val3179fs Pathogenic/Likely pathogenic ★★ same type
PCNT p.Arg143_Gln155dup Uncertain significance ★★ same type

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-cys2014fs (accessed [today's date]).

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