Is PCNT p.Ala2149= (c.6447G>T) pathogenic?

PCNT p.Ala2149= (c.6447G>T) is classified Likely benign in PCNT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-08). Very rare (popmax 6.2e-05%).

How common is PCNT p.Ala2149= (c.6447G>T) in the general population?

PCNT p.Ala2149= (c.6447G>T) is very rare (popmax 6.2e-05%) (gnomAD).

PCNT p.Ala2149=

c.6447G>T · rs763122571 · VCV3010104

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

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 -1.1	GERP -0.74, phastCons 0.001
Overall
CADD	0.648	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,614,078 alleles · very rare exomes 1/1,461,830 · genomes 0/152,248 · joint denominator

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.Ala2149=
Coding: c.6447G>T
MANE Select: NM_006031
dbSNP: rs763122571
Type: single nucleotide variant
Location: chr21:46416365 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)

Full PCNT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PCNT p.Ala2149Ser Uncertain significance ★ ⚠ same residue
PCNT p.Ala2149Thr Uncertain significance ★ ⚠ same residue
PCNT p.Ala2149Val Uncertain significance ⚠ same residue
PCNT p.Ala2149fs Pathogenic ★ same residue
PCNT c.1032+1G>A Pathogenic/Likely pathogenic ★★ same type
PCNT c.1680-1G>C Likely pathogenic ★★ same type
PCNT c.3313-2A>C Likely pathogenic ★★ same type
PCNT c.5995-2A>C Likely pathogenic ★★ same type

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-ala2149 (accessed [today's date]).

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