Is PCSK9 p.Ser47Phe (c.140C>T) pathogenic?

PCSK9 p.Ser47Phe (c.140C>T) is classified Uncertain significance in PCSK9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-14). AlphaMissense: likely benign (0.1523); No allele count reported in gnomAD v4.1 (AN 1,580,868); Associated with Cardiovascular phenotype.

What condition is associated with PCSK9 p.Ser47Phe (c.140C>T)?

PCSK9 p.Ser47Phe (c.140C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is PCSK9 p.Ser47Phe (c.140C>T) in the general population?

PCSK9 p.Ser47Phe (c.140C>T) is no allele count reported in gnomAD v4.1 (AN 1,580,868) (gnomAD).

What do computational predictors say about PCSK9 p.Ser47Phe (c.140C>T)?

AlphaMissense predicts likely benign (score 0.1523) — an in-silico prediction, not a clinical call.

PCSK9 p.Ser47Phe

c.140C>T · rs1372204035 · VCV3229294

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1523 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,580,868)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1523	likely benign
REVEL	0.112	moderately benign-leaning
SaProt	LLR -8.13	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.22	GERP 1
Regional constraint	o/e 0.91	unconstrained · MANE · 24 kb · p 0.0038 · regional, not allelic
Overall
CADD	16.02	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 and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,580,868). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PCSK9
Protein: p.Ser47Phe
Coding: c.140C>T
MANE Select: NM_174936
dbSNP: rs1372204035
Type: single nucleotide variant
Location: chr1:55039977 (GRCh38)
Gene constraint: LOEUF 1.25 · pLI <0.01 · ClinGen HI dosage-sensitivity unlikely (gnomAD)
Structure: AlphaFold pLDDT 85.03 · 66 PDB
Residue 47: a modified residue (phosphoserine; by fam20c)

Full PCSK9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PCSK9 p.Ser47= Conflicting classifications of pathogenicity ★ same residue
PCSK9 p.Ser47Tyr Uncertain significance ★ ⚠ same residue
PCSK9 p.Ser47Cys Pathogenic ⚠ same residue
PCSK9 p.Asp374His Pathogenic/Likely pathogenic ★★ ⚠ same condition
PCSK9 c.207+5G>A Uncertain significance ★★ same condition
PCSK9 p.Ala100Gly Uncertain significance ★★ ⚠ same condition
PCSK9 p.Ala220Thr Uncertain significance ★★ ⚠ same condition
PCSK9 p.Ala242Val 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/pcsk9-p-ser47phe (accessed [today's date]).

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