Is PCNT p.Pro179Ser (c.535C>T) pathogenic?

PCNT p.Pro179Ser (c.535C>T) is classified Uncertain significance in PCNT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-13). AlphaMissense: likely benign (0.1098); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PCNT p.Pro179Ser (c.535C>T)?

PCNT p.Pro179Ser (c.535C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PCNT p.Pro179Ser (c.535C>T) in the general population?

PCNT p.Pro179Ser (c.535C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PCNT p.Pro179Ser (c.535C>T)?

AlphaMissense predicts likely benign (score 0.1098) — an in-silico prediction, not a clinical call.

PCNT p.Pro179Ser

c.535C>T · VCV3886989

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1098 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1098	likely benign
REVEL	0.04	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 -0.53	GERP 0.086
Regional constraint	o/e 1.03	unconstrained · MANE · 121 kb · p 0.027 · regional, not allelic
Overall
CADD	0.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PCNT
Protein: p.Pro179Ser
Coding: c.535C>T
MANE Select: NM_006031
Type: single nucleotide variant
Location: chr21:46334664 (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.Pro179Leu Uncertain significance ★★ ⚠ same residue
PCNT p.Pro179= 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-pro179ser (accessed [today's date]).

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