Is PCNT p.Ala493= (c.1479G>A) pathogenic?

PCNT p.Ala493= (c.1479G>A) is classified Conflicting classifications of pathogenicity in PCNT (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-15). Ultra-rare (popmax 0.0245%, eas); Associated with microcephalic osteodysplastic primordial dwarfism type II.

What condition is associated with PCNT p.Ala493= (c.1479G>A)?

PCNT p.Ala493= (c.1479G>A) is associated with microcephalic osteodysplastic primordial dwarfism type II (ClinVar).

How common is PCNT p.Ala493= (c.1479G>A) in the general population?

PCNT p.Ala493= (c.1479G>A) is ultra-rare (popmax 0.0245%, eas) (gnomAD).

PCNT p.Ala493=

c.1479G>A · rs199864153 · VCV340472

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, 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 -7.2	GERP -3.3
Overall
CADD	0.906	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0245% East Asian · 11/44,898 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00335% 54/1,613,870 alleles · ultra-rare exomes 52/1,461,646 · genomes 2/152,224 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0245%	4,082
Admixed American	0.00833%	12,001
Remaining individualsnot grpmax-eligible	0.0048%	20,828
European (non-Finnish)	0.0028%	35,758
South Asian	0.0022%	45,546

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.Ala493=
Coding: c.1479G>A
MANE Select: NM_006031
dbSNP: rs199864153
Type: single nucleotide variant
Location: chr21:46353126 (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-ala493 (accessed [today's date]).

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