Is PCNT p.Ser463Ter (c.1388C>G) pathogenic?

PCNT p.Ser463Ter (c.1388C>G) is classified Pathogenic in PCNT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-18). Very rare (popmax 0.000339%, nfe).

How common is PCNT p.Ser463Ter (c.1388C>G) in the general population?

PCNT p.Ser463Ter (c.1388C>G) is very rare (popmax 0.000339%, nfe) (gnomAD).

PCNT p.Ser463Ter

c.1388C>G · rs770995623 · VCV2737011

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 47
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Pangolin	Δ0.34	loss · gain 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 7.1	GERP 1.8, phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,362 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,613,292 alleles · very rare exomes 2/1,461,114 · genomes 2/152,178 · 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.Ser463Ter
Coding: c.1388C>G
MANE Select: NM_006031
dbSNP: rs770995623
Type: single nucleotide variant
Location: chr21:46351472 (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 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
PCNT c.7024+1G>A Likely pathogenic ★★ same type
PCNT c.7024+1G>C Likely pathogenic ★★ same type
PCNT c.7691-1G>A Likely pathogenic ★★ same type
PCNT c.8065-1G>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-ser463ter (accessed [today's date]).

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