Is PCNT p.Arg1903= (c.5709C>T) pathogenic?

PCNT p.Arg1903= (c.5709C>T) is classified Likely benign in PCNT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-15). Very rare (popmax 0.00802%, afr).

How common is PCNT p.Arg1903= (c.5709C>T) in the general population?

PCNT p.Arg1903= (c.5709C>T) is very rare (popmax 0.00802%, afr) (gnomAD).

PCNT p.Arg1903=

c.5709C>T · rs774766182 · VCV1013199

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00802%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.4	GERP -5.1
Overall
CADD	0.187	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00802% African / African-American · 6/74,788 alleles

Filtering AF 0.00348% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.00181% 29/1,602,922 alleles · very rare exomes 26/1,450,680 · genomes 3/152,242 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00802%	12,465
South Asian	0.0022%	45,395
European (non-Finnish)	0.0017%	58,863
Remaining individualsnot grpmax-eligible	0.00161%	62,090

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.Arg1903=
Coding: c.5709C>T
MANE Select: NM_006031
dbSNP: rs774766182
Type: single nucleotide variant
Location: chr21:46411782 (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.Arg1903Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
PCNT p.Arg1903His Conflicting classifications of pathogenicity ★ ⚠ same residue
PCNT p.Arg1903Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
PCNT p.Arg1903Phe 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

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-arg1903 (accessed [today's date]).

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