Is PCNT p.Pro2368= (c.7104T>C) pathogenic?

PCNT p.Pro2368= (c.7104T>C) is classified Conflicting classifications of pathogenicity in PCNT (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-11-24). Ultra-rare (popmax 0.0933%, sas); Associated with microcephalic osteodysplastic primordial dwarfism type II.

What condition is associated with PCNT p.Pro2368= (c.7104T>C)?

PCNT p.Pro2368= (c.7104T>C) is associated with microcephalic osteodysplastic primordial dwarfism type II (ClinVar).

How common is PCNT p.Pro2368= (c.7104T>C) in the general population?

PCNT p.Pro2368= (c.7104T>C) is ultra-rare (popmax 0.0933%, sas) (gnomAD).

PCNT p.Pro2368=

c.7104T>C · rs576187743 · VCV211877

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0933%, sas)

Conditions

microcephalic osteodysplastic primordial dwarfism type II

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 -0.75	GERP -1.1
Overall
CADD	0.833	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0933% South Asian · 85/91,086 alleles

Filtering AF 0.0773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0713%

Overall 0.007% 113/1,614,022 alleles · ultra-rare exomes 109/1,461,702 · genomes 4/152,320 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0933%	1,072
Middle Eastern	0.066%	1,516
Remaining individualsnot grpmax-eligible	0.0112%	8,929
European (non-Finnish)	0.00144%	69,412

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.Pro2368=
Coding: c.7104T>C
MANE Select: NM_006031
dbSNP: rs576187743
Type: single nucleotide variant
Location: chr21:46422049 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)
Residue 2368: the 'disordered' region

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

Disease context

microcephalic osteodysplastic primordial dwarfism type II — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PCNT c.1032+1G>A Pathogenic/Likely pathogenic ★★ same condition
PCNT c.1680-1G>C Likely pathogenic ★★ same condition
PCNT c.5995-2A>C Likely pathogenic ★★ same condition
PCNT c.7024+1G>C Likely pathogenic ★★ same condition
PCNT c.7691-1G>A Likely pathogenic ★★ same condition
PCNT c.9624-2A>G Likely pathogenic ★★ same condition
PCNT p.Arg1730Ter Pathogenic/Likely pathogenic ★★ same condition
PCNT p.Arg1923Ter Pathogenic/Likely pathogenic ★★ 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-pro2368 (accessed [today's date]).

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