Is PCNT p.Pro1524= (c.4572G>A) pathogenic?

PCNT p.Pro1524= (c.4572G>A) is classified Benign in PCNT (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-31). Low-frequency (popmax 2.67%, afr); Associated with microcephalic osteodysplastic primordial dwarfism type II.

What condition is associated with PCNT p.Pro1524= (c.4572G>A)?

PCNT p.Pro1524= (c.4572G>A) is associated with microcephalic osteodysplastic primordial dwarfism type II (ClinVar).

How common is PCNT p.Pro1524= (c.4572G>A) in the general population?

PCNT p.Pro1524= (c.4572G>A) is low-frequency (popmax 2.67%, afr) (gnomAD).

PCNT p.Pro1524=

c.4572G>A · rs116431741 · VCV159606

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.67%, afr)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.27	GERP -4.7, phastCons 0.001
Overall
CADD	6.309	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.67% African / African-American · 1,999/74,942 alleles

Filtering AF 2.57% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.53%

Overall 0.15% 2,407/1,606,806 alleles · low-frequency exomes 1,277/1,454,462 · genomes 1,130/152,344 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.67%	37
Middle Eastern	0.202%	495
Remaining individualsnot grpmax-eligible	0.182%	549
Admixed American	0.172%	581
East Asian	0.0179%	5,588
European (non-Finnish)	0.0141%	7,095
South Asian	0.0111%	9,009

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.Pro1524=
Coding: c.4572G>A
MANE Select: NM_006031
dbSNP: rs116431741
Type: single nucleotide variant
Location: chr21:46398243 (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

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

Similar variants

PCNT p.Pro1524Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
PCNT p.Pro1524Leu Uncertain significance ★ ⚠ same residue
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

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-pro1524 (accessed [today's date]).

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