Is PCNT p.Ala955= (c.2865C>T) pathogenic?

PCNT p.Ala955= (c.2865C>T) is classified Benign/Likely benign in PCNT (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-25). Rare (popmax 0.971%, sas); Associated with microcephalic osteodysplastic primordial dwarfism type II.

What condition is associated with PCNT p.Ala955= (c.2865C>T)?

PCNT p.Ala955= (c.2865C>T) is associated with microcephalic osteodysplastic primordial dwarfism type II (ClinVar).

How common is PCNT p.Ala955= (c.2865C>T) in the general population?

PCNT p.Ala955= (c.2865C>T) is rare (popmax 0.971%, sas) (gnomAD).

PCNT p.Ala955=

c.2865C>T · rs540548340 · VCV211850

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.971%, 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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -10	GERP -17
Overall
CADD	0.033	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.971% South Asian · 884/91,082 alleles

Filtering AF 0.917% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.896%

Overall 0.0585% 945/1,614,008 alleles · rare exomes 892/1,461,642 · genomes 53/152,366 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.971%	103
Remaining individualsnot grpmax-eligible	0.072%	1,389
Middle Eastern	0.0495%	2,020
Admixed American	0.005%	20,011
African / African-American	0.004%	25,023
East Asian	0.00223%	44,880
European (non-Finnish)	0.000508%	196,675

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.Ala955=
Coding: c.2865C>T
MANE Select: NM_006031
dbSNP: rs540548340
Type: single nucleotide variant
Location: chr21:46366839 (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-ala955 (accessed [today's date]).

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