Is PCNT p.Arg1845= (c.5535G>A) pathogenic?

PCNT p.Arg1845= (c.5535G>A) is classified Benign in PCNT (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 17.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with microcephalic osteodysplastic primordial dwarfism type II.

What condition is associated with PCNT p.Arg1845= (c.5535G>A)?

PCNT p.Arg1845= (c.5535G>A) is associated with microcephalic osteodysplastic primordial dwarfism type II (ClinVar).

PCNT p.Arg1845=

Q: How common is PCNT p.Arg1845= (c.5535G>A) in the general population?

PCNT p.Arg1845= (c.5535G>A) is common (popmax 17.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.5535G>A · rs61735543 · VCV138620

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 17.5%, afr) — too common for a highly-penetrant pathogenic allele

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 2.2	GERP -0.002, phastCons 0.99
Overall
CADD	4.092	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 17.5% African / African-American · 13,152/74,992 alleles

Filtering AF 17.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 17.2%

Overall 2.27% 36,653/1,613,006 alleles · common exomes 27,402/1,460,716 · genomes 9,251/152,290 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	17.5%	6
South Asian	7.13%	14
Remaining individualsnot grpmax-eligible	2.96%	34
Middle Eastern	2.59%	39
Admixed American	2.22%	45
Finnishnot grpmax-eligible	2.07%	48
Ashkenazi Jewishnot grpmax-eligible	1.33%	75
European (non-Finnish)	1.01%	99
East Asian	0.201%	499

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.Arg1845=
Coding: c.5535G>A
MANE Select: NM_006031
dbSNP: rs61735543
Type: single nucleotide variant
Location: chr21:46411608 (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 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-arg1845 (accessed [today's date]).

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