Is PCNT p.Asp2343= (c.7029C>T) pathogenic?

PCNT p.Asp2343= (c.7029C>T) is classified Conflicting classifications of pathogenicity in PCNT (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-02-17). Ultra-rare (popmax 0.011%, sas); Associated with microcephalic osteodysplastic primordial dwarfism type II.

What condition is associated with PCNT p.Asp2343= (c.7029C>T)?

PCNT p.Asp2343= (c.7029C>T) is associated with microcephalic osteodysplastic primordial dwarfism type II (ClinVar).

How common is PCNT p.Asp2343= (c.7029C>T) in the general population?

PCNT p.Asp2343= (c.7029C>T) is ultra-rare (popmax 0.011%, sas) (gnomAD).

PCNT p.Asp2343=

c.7029C>T · rs143064269 · VCV898797

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, 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	<0.2	all four deltas below 0.2 · C>G here scores Δ0.37 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.9	GERP -4.3
Overall
CADD	0.193	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.011% South Asian · 10/91,090 alleles

Filtering AF 0.00766% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00708%

Overall 0.00787% 127/1,613,900 alleles · ultra-rare exomes 119/1,461,724 · genomes 8/152,176 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.011%	9,109
European (non-Finnish)	0.00907%	11,028
Remaining individualsnot grpmax-eligible	0.0064%	15,620
East Asian	0.00446%	22,434
Admixed American	0.00333%	30,001
African / African-American	0.00267%	37,461

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.Asp2343=
Coding: c.7029C>T
MANE Select: NM_006031
dbSNP: rs143064269
Type: single nucleotide variant
Location: chr21:46421974 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)
Residue 2343: 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-asp2343 (accessed [today's date]).

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