Is PCNT p.Ser2267Pro (c.6799T>C) pathogenic?

PCNT p.Ser2267Pro (c.6799T>C) is classified Uncertain significance in PCNT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-12). AlphaMissense: likely benign (0.0807); Very rare (popmax 0.00172%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PCNT p.Ser2267Pro (c.6799T>C)?

PCNT p.Ser2267Pro (c.6799T>C) is associated with Inborn genetic diseases (ClinVar).

How common is PCNT p.Ser2267Pro (c.6799T>C) in the general population?

PCNT p.Ser2267Pro (c.6799T>C) is very rare (popmax 0.00172%, nfe) (gnomAD).

What do computational predictors say about PCNT p.Ser2267Pro (c.6799T>C)?

AlphaMissense predicts likely benign (score 0.0807) — an in-silico prediction, not a clinical call.

PCNT p.Ser2267Pro

c.6799T>C · rs1344945821 · VCV2892243

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0807 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00172%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0807	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.74	GERP -5.4, phastCons 0.008
Regional constraint	o/e 1.03	unconstrained · MANE · 121 kb · p 0.027 · regional, not allelic
Overall
CADD	6.93	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00172% European (non-Finnish) · 20/1,160,264 alleles

Filtering AF 0.00113% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000915%

Overall 0.00127% 20/1,578,674 alleles · very rare exomes 17/1,426,528 · genomes 3/152,146 · 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.Ser2267Pro
Coding: c.6799T>C
MANE Select: NM_006031
dbSNP: rs1344945821
Type: single nucleotide variant
Location: chr21:46416717 (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.Ser2267Leu Uncertain significance ★★ ⚠ same residue
PCNT p.Ser2267= Likely benign ★ same residue
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

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-ser2267pro (accessed [today's date]).

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