Is PCNT p.Lys18= (c.54G>A) pathogenic?

PCNT p.Lys18= (c.54G>A) is classified Uncertain significance in PCNT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-11). Very rare (popmax 0.00238%, nfe); Associated with PCNT-related disorder.

What condition is associated with PCNT p.Lys18= (c.54G>A)?

PCNT p.Lys18= (c.54G>A) is associated with PCNT-related disorder (ClinVar).

How common is PCNT p.Lys18= (c.54G>A) in the general population?

PCNT p.Lys18= (c.54G>A) is very rare (popmax 0.00238%, nfe) (gnomAD).

PCNT p.Lys18=

c.54G>A · rs367711247 · VCV2634215

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00238%, nfe)

Conditions

PCNT-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.61	donor loss · deltas
Pangolin	Δ0.60	loss · gain 0.07 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00238% European (non-Finnish) · 28/1,177,798 alleles

Filtering AF 0.00165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00205% 33/1,609,724 alleles · very rare exomes 30/1,457,474 · genomes 3/152,250 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00643%	15,555
European (non-Finnish)grpmax	0.00238%	42,064
African / African-American	0.00134%	74,870

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Lys18=
Coding: c.54G>A
MANE Select: NM_006031
dbSNP: rs367711247
Type: single nucleotide variant
Location: chr21:46324282 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)
Residue 18: the 'disordered' region

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

Disease context

PCNT-related disorder

Similar variants

PCNT c.3313-2A>C Likely pathogenic ★★ same condition
PCNT c.7024+1G>A Likely pathogenic ★★ same condition
PCNT c.7691-1G>A Likely pathogenic ★★ same condition
PCNT c.8065-1G>C Likely pathogenic ★★ same condition
PCNT p.Arg3236Ter Pathogenic/Likely pathogenic ★★ same condition
PCNT p.Gln1689Ter Likely pathogenic ★★ same condition
PCNT p.Gln490Ter Pathogenic ★★ same condition
PCNT p.Ala1879Gly 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-lys18 (accessed [today's date]).

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