Is PCNT p.Ala3058= (c.9174G>A) pathogenic?

PCNT p.Ala3058= (c.9174G>A) is classified Benign/Likely benign in PCNT (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-09-24). Rare (popmax 0.649%, sas); Associated with microcephalic osteodysplastic primordial dwarfism type II.

What condition is associated with PCNT p.Ala3058= (c.9174G>A)?

PCNT p.Ala3058= (c.9174G>A) is associated with microcephalic osteodysplastic primordial dwarfism type II (ClinVar).

How common is PCNT p.Ala3058= (c.9174G>A) in the general population?

PCNT p.Ala3058= (c.9174G>A) is rare (popmax 0.649%, sas) (gnomAD).

PCNT p.Ala3058=

c.9174G>A · rs554275370 · VCV159688

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.649%, 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.
REVEL	0.015	strongly benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -12	GERP -4.6
Overall
CADD	0.068	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.649% South Asian · 591/91,090 alleles

Filtering AF 0.606% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.588%

Overall 0.04% 646/1,614,102 alleles · rare exomes 613/1,461,788 · genomes 33/152,314 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.649%	154
Remaining individualsnot grpmax-eligible	0.0352%	2,841
Middle Eastern	0.033%	3,031
African / African-American	0.00666%	15,008
European (non-Finnish)	0.00212%	47,198
Admixed American	0.00167%	60,028

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.Ala3058=
Coding: c.9174G>A
MANE Select: NM_006031
dbSNP: rs554275370
Type: single nucleotide variant
Location: chr21:46438238 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)
Residue 3058: the 'interaction with nek2' 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 p.Ala3058Val Uncertain significance ★★ ⚠ same residue
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

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-ala3058 (accessed [today's date]).

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