Is PCNT p.Ala2292= (c.6876C>T) pathogenic?

PCNT p.Ala2292= (c.6876C>T) is classified Conflicting classifications of pathogenicity in PCNT (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-04-09). Ultra-rare (popmax 0.0204%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PCNT p.Ala2292= (c.6876C>T)?

PCNT p.Ala2292= (c.6876C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PCNT p.Ala2292= (c.6876C>T) in the general population?

PCNT p.Ala2292= (c.6876C>T) is ultra-rare (popmax 0.0204%, nfe) (gnomAD).

PCNT p.Ala2292=

c.6876C>T · rs761995771 · VCV288217

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0204%, nfe)

Conditions

Inborn genetic diseases

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 -1.9	GERP -5.4
Overall
CADD	0.38	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0204% European (non-Finnish) · 240/1,179,174 alleles

Filtering AF 0.0182% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0174%

Overall 0.0158% 253/1,600,532 alleles · ultra-rare exomes 240/1,448,318 · genomes 13/152,214 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0204%	4,913
Remaining individualsnot grpmax-eligible	0.0144%	6,921
African / African-American	0.00534%	18,725

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.Ala2292=
Coding: c.6876C>T
MANE Select: NM_006031
dbSNP: rs761995771
Type: single nucleotide variant
Location: chr21:46416794 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PCNT p.Gln910Ter Pathogenic ★★ same condition
PCNT p.Ala1194Val Uncertain significance ★★ ⚠ same condition
PCNT p.Ala1400Thr Uncertain significance ★★ ⚠ same condition
PCNT p.Ala1457Val Uncertain significance ★★ ⚠ same condition
PCNT p.Ala1827Ser Uncertain significance ★★ ⚠ same condition
PCNT p.Ala1827Thr Uncertain significance ★★ ⚠ same condition
PCNT p.Ala1831Val Uncertain significance ★★ ⚠ same condition
PCNT p.Ala1964Val Uncertain significance ★★ ⚠ 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-ala2292 (accessed [today's date]).

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