Is PCNT p.Arg1492= (c.4476C>T) pathogenic?

PCNT p.Arg1492= (c.4476C>T) is classified Likely benign in PCNT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-01). Very rare (popmax 0.00162%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PCNT p.Arg1492= (c.4476C>T)?

PCNT p.Arg1492= (c.4476C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PCNT p.Arg1492= (c.4476C>T) in the general population?

PCNT p.Arg1492= (c.4476C>T) is very rare (popmax 0.00162%, nfe) (gnomAD).

PCNT p.Arg1492=

c.4476C>T · rs1207865290 · VCV2968239

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00162%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -8.9	GERP -4.8
Overall
CADD	1.057	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00162% European (non-Finnish) · 19/1,171,114 alleles

Filtering AF 0.00104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000836%

Overall 0.00119% 19/1,593,068 alleles · very rare exomes 17/1,440,854 · genomes 2/152,214 · 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.Arg1492=
Coding: c.4476C>T
MANE Select: NM_006031
dbSNP: rs1207865290
Type: single nucleotide variant
Location: chr21:46398043 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PCNT p.Arg1492His Uncertain significance ★ same residue
PCNT p.Arg1492Cys Uncertain significance ★ same residue
PCNT p.Gln910Ter Pathogenic ★★ same condition
PCNT p.Ala1194Val Uncertain significance ★★ ⚠ same condition
PCNT p.Ala1400Thr Uncertain significance ★★ ⚠ same condition
PCNT p.Ala1457Val Uncertain significance ★★ ⚠ same condition
PCNT p.Ala1827Ser Uncertain significance ★★ ⚠ same condition
PCNT p.Ala1827Thr Uncertain significance ★★ ⚠ 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-arg1492 (accessed [today's date]).

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