Is PCNT p.Asp2945= (c.8835C>T) pathogenic?

PCNT p.Asp2945= (c.8835C>T) is classified Likely benign in PCNT (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-26). Ultra-rare (popmax 0.0839%, afr); Associated with microcephalic osteodysplastic primordial dwarfism type II.

What condition is associated with PCNT p.Asp2945= (c.8835C>T)?

PCNT p.Asp2945= (c.8835C>T) is associated with microcephalic osteodysplastic primordial dwarfism type II (ClinVar).

How common is PCNT p.Asp2945= (c.8835C>T) in the general population?

PCNT p.Asp2945= (c.8835C>T) is ultra-rare (popmax 0.0839%, afr) (gnomAD).

PCNT p.Asp2945=

c.8835C>T · rs146875945 · VCV1337232

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0839%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.067	GERP -3.7
Overall
CADD	2.313	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0839% African / African-American · 63/75,068 alleles

Filtering AF 0.0673% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0612%

Overall 0.00582% 94/1,614,154 alleles · ultra-rare exomes 50/1,461,810 · genomes 44/152,344 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0839%	1,192
Middle Eastern	0.0165%	6,062
Admixed American	0.00833%	12,006
Finnishnot grpmax-eligible	0.00781%	12,800
South Asian	0.00329%	30,362
Remaining individualsnot grpmax-eligible	0.0032%	31,252
East Asian	0.00223%	44,856
European (non-Finnish)	0.00119%	84,288

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.Asp2945=
Coding: c.8835C>T
MANE Select: NM_006031
dbSNP: rs146875945
Type: single nucleotide variant
Location: chr21:46435987 (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.Asp2945Gly 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
PCNT p.Arg1730Ter 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-asp2945 (accessed [today's date]).

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