Is PCNT p.Arg507Ter (c.1519C>T) pathogenic?

PCNT p.Arg507Ter (c.1519C>T) is classified Pathogenic in PCNT (ClinVar, Single submitter, 2 submitters; last evaluated 2023-04-07). Very rare (popmax 0.00133%, afr).

How common is PCNT p.Arg507Ter (c.1519C>T) in the general population?

PCNT p.Arg507Ter (c.1519C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

PCNT p.Arg507Ter

c.1519C>T · rs138036524 · VCV1453798

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 47
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP 1.7, phastCons 0.001
Overall
CADD	34.0	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 0.00133% African / African-American · 1/75,018 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000805% 13/1,614,026 alleles · very rare exomes 13/1,461,778 · genomes 0/152,248 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,018
South Asian	0.0011%	91,080
European (non-Finnish)	0.000932%	107,275

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.Arg507Ter
Coding: c.1519C>T
MANE Select: NM_006031
dbSNP: rs138036524
Type: single nucleotide variant
Location: chr21:46353166 (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.Arg507Gly Likely benign ★★ same residue
PCNT p.Arg507Gln Uncertain significance ⚠ same residue
PCNT c.1032+1G>A Pathogenic/Likely pathogenic ★★ same type
PCNT c.1680-1G>C Likely pathogenic ★★ same type
PCNT c.3313-2A>C Likely pathogenic ★★ same type
PCNT c.5995-2A>C Likely pathogenic ★★ same type
PCNT c.7024+1G>A Likely pathogenic ★★ same type
PCNT c.7024+1G>C Likely pathogenic ★★ 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-arg507ter (accessed [today's date]).

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