Is PCNT p.Ala2600= (c.7800G>A) pathogenic?

PCNT p.Ala2600= (c.7800G>A) is classified Benign in PCNT (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-01). Low-frequency (popmax 2.55%, nfe); Associated with microcephalic osteodysplastic primordial dwarfism type II.

What condition is associated with PCNT p.Ala2600= (c.7800G>A)?

PCNT p.Ala2600= (c.7800G>A) is associated with microcephalic osteodysplastic primordial dwarfism type II (ClinVar).

How common is PCNT p.Ala2600= (c.7800G>A) in the general population?

PCNT p.Ala2600= (c.7800G>A) is low-frequency (popmax 2.55%, nfe) (gnomAD).

PCNT p.Ala2600=

c.7800G>A · rs61735820 · VCV138606

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.55%, nfe)

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 0.14	GERP -3.7
Overall
CADD	3.91	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.55% European (non-Finnish) · 30,118/1,179,990 alleles

Filtering AF 2.53% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.52%

Overall 2.05% 33,143/1,614,180 alleles · low-frequency exomes 30,931/1,461,836 · genomes 2,212/152,344 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	2.55%	39
Remaining individualsnot grpmax-eligible	1.68%	59
Admixed American	1%	100
Finnishnot grpmax-eligible	0.781%	128
Ashkenazi Jewishnot grpmax-eligible	0.557%	179
Middle Eastern	0.528%	189
South Asian	0.423%	237
African / African-American	0.384%	261
Amishnot grpmax-eligible	0.11%	912

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.Ala2600=
Coding: c.7800G>A
MANE Select: NM_006031
dbSNP: rs61735820
Type: single nucleotide variant
Location: chr21:46430119 (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 p.Ala2600Val 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-ala2600 (accessed [today's date]).

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