Is PROKR2 p.Arg271Ser (c.813G>T) pathogenic?

PROKR2 p.Arg271Ser (c.813G>T) is classified Uncertain significance in PROKR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-12). AlphaMissense: likely pathogenic (0.9525); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PROKR2 p.Arg271Ser (c.813G>T)?

PROKR2 p.Arg271Ser (c.813G>T) is associated with Inborn genetic diseases (ClinVar).

How common is PROKR2 p.Arg271Ser (c.813G>T) in the general population?

PROKR2 p.Arg271Ser (c.813G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PROKR2 p.Arg271Ser (c.813G>T)?

AlphaMissense predicts likely pathogenic (score 0.9525) — an in-silico prediction, not a clinical call.

PROKR2 p.Arg271Ser

c.813G>T · VCV3425614

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9525 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9525	likely pathogenic · top 8% in PROKR2
REVEL	0.6	indeterminate
SaProt	LLR -12.88	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.35	GERP -1.5, phastCons 0.066
Regional constraint	o/e 0.89	unconstrained · MANE · 12 kb · p 0.0097 · regional, not allelic
Overall
CADD	22.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: PROKR2
Protein: p.Arg271Ser
Coding: c.813G>T
MANE Select: NM_144773
Type: single nucleotide variant
Location: chr20:5302382 (GRCh38)
Gene constraint: LOEUF 1.492 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.50

Full PROKR2 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

PROKR2 p.Arg47Gln Uncertain significance ★★ ⚠ same condition
PROKR2 p.Glu377Lys Uncertain significance ★★ ⚠ same condition
PROKR2 p.Gly70Ser Uncertain significance ★★ same condition
PROKR2 p.Ile56Thr Uncertain significance ★★ ⚠ same condition
PROKR2 p.Met179Ile Uncertain significance ★★ ⚠ same condition
PROKR2 p.Pro17His Uncertain significance ★★ ⚠ same condition
PROKR2 p.Ser130= Likely benign ★★ same condition
PROKR2 p.Ala170Val 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/prokr2-p-arg271ser (accessed [today's date]).

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