Is PCNT p.His369= (c.1107T>C) pathogenic?

PCNT p.His369= (c.1107T>C) is classified Conflicting classifications of pathogenicity in PCNT (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-07-02). Rare (popmax 0.27%, afr); Associated with microcephalic osteodysplastic primordial dwarfism type II.

What condition is associated with PCNT p.His369= (c.1107T>C)?

PCNT p.His369= (c.1107T>C) is associated with microcephalic osteodysplastic primordial dwarfism type II (ClinVar).

How common is PCNT p.His369= (c.1107T>C) in the general population?

PCNT p.His369= (c.1107T>C) is rare (popmax 0.27%, afr) (gnomAD).

PCNT p.His369=

c.1107T>C · rs113731555 · VCV340467

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.27%, 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 -0.36	GERP -3.9, phastCons 0.2
Overall
CADD	6.256	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.27% African / African-American · 202/74,936 alleles

Filtering AF 0.239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.227%

Overall 0.0149% 239/1,608,474 alleles · rare exomes 128/1,456,170 · genomes 111/152,304 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.27%	371
Remaining individualsnot grpmax-eligible	0.0353%	2,833
Admixed American	0.0217%	4,617
South Asian	0.0022%	45,480

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.His369=
Coding: c.1107T>C
MANE Select: NM_006031
dbSNP: rs113731555
Type: single nucleotide variant
Location: chr21:46349086 (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-his369 (accessed [today's date]).

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