Is PCNT p.Ala385= (c.1155A>G) pathogenic?

PCNT p.Ala385= (c.1155A>G) is classified Conflicting classifications of pathogenicity in PCNT (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-04-01). Rare (popmax 0.334%, eas); Associated with microcephalic osteodysplastic primordial dwarfism type II.

What condition is associated with PCNT p.Ala385= (c.1155A>G)?

PCNT p.Ala385= (c.1155A>G) is associated with microcephalic osteodysplastic primordial dwarfism type II (ClinVar).

How common is PCNT p.Ala385= (c.1155A>G) in the general population?

PCNT p.Ala385= (c.1155A>G) is rare (popmax 0.334%, eas) (gnomAD).

PCNT p.Ala385=

c.1155A>G · rs201944549 · VCV340468

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.334%, eas)

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 -1.1	GERP -3.9
Overall
CADD	6.478	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.334% East Asian · 150/44,890 alleles

Filtering AF 0.29% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.274%

Overall 0.01% 162/1,613,916 alleles · rare exomes 143/1,461,536 · genomes 19/152,380 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.334%	299
Remaining individualsnot grpmax-eligible	0.0112%	8,929
South Asian	0.00329%	30,357
European (non-Finnish)	0.00017%	589,873

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.Ala385=
Coding: c.1155A>G
MANE Select: NM_006031
dbSNP: rs201944549
Type: single nucleotide variant
Location: chr21:46349134 (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-ala385 (accessed [today's date]).

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