Is PCNT p.Arg585Ter (c.1753C>T) pathogenic?

PCNT p.Arg585Ter (c.1753C>T) is classified Pathogenic in PCNT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-29). Very rare (popmax 0.00333%, amr).

How common is PCNT p.Arg585Ter (c.1753C>T) in the general population?

PCNT p.Arg585Ter (c.1753C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

PCNT p.Arg585Ter

c.1753C>T · rs1360157605 · VCV2713446

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

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 11 of 47
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.2	GERP 1.5, phastCons 1
Overall
CADD	35.0	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 0.00333% Admixed American · 2/60,000 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000434% 7/1,613,802 alleles · very rare exomes 6/1,461,620 · genomes 1/152,182 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,000
European (non-Finnish)	0.000424%	235,970

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.Arg585Ter
Coding: c.1753C>T
MANE Select: NM_006031
dbSNP: rs1360157605
Type: single nucleotide variant
Location: chr21:46354060 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)
Residue 585: the 'disordered' region

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

Similar variants

PCNT p.Arg585Gln Likely benign ★ 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
PCNT c.7691-1G>A 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-arg585ter (accessed [today's date]).

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