Is PROK2 p.Ser119= (c.357A>G) pathogenic?

PROK2 p.Ser119= (c.357A>G) is classified Likely benign in PROK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-01). Absent from gnomAD v4.1.

How common is PROK2 p.Ser119= (c.357A>G) in the general population?

PROK2 p.Ser119= (c.357A>G) is absent from gnomAD v4.1 (gnomAD).

PROK2 p.Ser119=

c.357A>G · VCV4887616

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.8	GERP -4.8
Overall
CADD	1.325	PHRED · no single calibrated threshold — expert panels disagree

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: PROK2
Protein: p.Ser119=
Coding: c.357A>G
MANE Select: NM_001126128
Type: single nucleotide variant
Location: chr3:71772757 (GRCh38)
Gene constraint: LOEUF 1.052 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 69.22

Full PROK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PROK2 p.Arg101Gln Uncertain significance ★★ ⚠ same type
PROK2 p.Arg101Trp Uncertain significance ★★ ⚠ same type
PROK2 p.Arg122Gln Uncertain significance ★★ ⚠ same type
PROK2 p.Asp66Asn Uncertain significance ★★ ⚠ same type
PROK2 p.Gly62Asp Uncertain significance ★★ ⚠ same type
PROK2 p.Val29Met Uncertain significance ★★ ⚠ same type
PROK2 c.285+14G>A Benign ★★ same type
PROK2 c.-35A>G 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/prok2-p-ser119 (accessed [today's date]).

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