Is PCNA p.Ser170Cys (c.509C>G) pathogenic?

PCNA p.Ser170Cys (c.509C>G) is classified Uncertain significance in PCNA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely benign (0.1902); Absent from gnomAD v4.1.

How common is PCNA p.Ser170Cys (c.509C>G) in the general population?

PCNA p.Ser170Cys (c.509C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PCNA p.Ser170Cys (c.509C>G)?

AlphaMissense predicts likely benign (score 0.1902) — an in-silico prediction, not a clinical call.

PCNA p.Ser170Cys

c.509C>G · VCV4535614

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1902 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1902	likely benign
REVEL	0.748	pathogenic-leaning
SaProt	LLR -8.65	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.92, phastCons 1
Regional constraint	o/e 0.50	unconstrained · MANE · 4,512 bp · p 2.9e-19 · regional, not allelic
Overall
CADD	28.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: PCNA
Protein: p.Ser170Cys
Coding: c.509C>G
MANE Select: NM_182649
Type: single nucleotide variant
Location: chr20:5117543 (GRCh38)
Gene constraint: LOEUF 0.42 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 94.38 · 103 PDB
Residue 170: a β-strand

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

Similar variants

PCNA p.Cys148Ser Likely pathogenic ★★ same type
PCNA p.Ser228Ile Uncertain significance ★★ ⚠ same type
PCNA p.Ala242= Benign/Likely benign ★★ same type
PCNA p.Pro234= Benign ★★ same type
PCNA p.Arg53Gln Uncertain significance ★ ⚠ same type
PCNA p.Asn24Ser Uncertain significance ★ ⚠ same type
PCNA p.Gly56Ser Uncertain significance ★ ⚠ same type
PCNA p.Leu182Phe Uncertain significance ★ ⚠ 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/pcna-p-ser170cys (accessed [today's date]).

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