Is PCNT p.Ser3172fs (c.9510_9511del) pathogenic?

PCNT p.Ser3172fs (c.95109511del) is classified Pathogenic in PCNT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-18). Ultra-rare (popmax 0.0165%, mid).

How common is PCNT p.Ser3172fs (c.9510_9511del) in the general population?

PCNT p.Ser3172fs (c.9510_9511del) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

PCNT p.Ser3172fs

c.9510_9511del · rs773316940 · VCV2801131

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 43 of 47
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.063	phastCons 0.01

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,060 alleles

Overall 0.000186% 3/1,613,566 alleles · ultra-rare exomes 3/1,461,234 · genomes 0/152,332 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	8.48e-05%	1,179,444

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.Ser3172fs
Coding: c.9510_9511del
MANE Select: NM_006031
dbSNP: rs773316940
Type: Microsatellite
Location: chr21:46440969 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)
Residue 3172: the 'interaction with nek2' region

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

Similar variants

PCNT p.Arg2865fs Pathogenic ★★ same type
PCNT p.Arg388fs Pathogenic ★★ same type
PCNT p.Cys2614_Glu2615delinsTer Pathogenic/Likely pathogenic ★★ same type
PCNT p.His1288fs Pathogenic/Likely pathogenic ★★ same type
PCNT p.Leu1007fs Pathogenic ★★ same type
PCNT p.Ser1142fs Pathogenic/Likely pathogenic ★★ same type
PCNT p.Val557fs Pathogenic ★★ same type
PCNT c.4446+17_4446+19del Likely benign ★★ 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-ser3172fs (accessed [today's date]).

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