Is PRG4 p.Pro514Arg (c.1541C>G) pathogenic?

PRG4 p.Pro514Arg (c.1541C>G) is classified Uncertain significance in PRG4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-23). AlphaMissense: likely benign (0.1715); Very rare (popmax 8.53e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PRG4 p.Pro514Arg (c.1541C>G)?

PRG4 p.Pro514Arg (c.1541C>G) is associated with Inborn genetic diseases (ClinVar).

How common is PRG4 p.Pro514Arg (c.1541C>G) in the general population?

PRG4 p.Pro514Arg (c.1541C>G) is very rare (popmax 8.53e-05%, nfe) (gnomAD).

What do computational predictors say about PRG4 p.Pro514Arg (c.1541C>G)?

AlphaMissense predicts likely benign (score 0.1715) — an in-silico prediction, not a clinical call.

PRG4 p.Pro514Arg

c.1541C>G · VCV3783210

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1715 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.53e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1715	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -11.94	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.04	GERP -0.52
Regional constraint	o/e 0.93	unconstrained · MANE · 6,664 bp · p 0.015 · regional, not allelic
Overall
CADD	15.0	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

Grpmax group 8.53e-05% European (non-Finnish) · 1/1,172,336 alleles

Overall 6.27e-05% 1/1,593,976 alleles · very rare exomes 1/1,455,114 · genomes 0/138,862 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PRG4
Protein: p.Pro514Arg
Coding: c.1541C>G
MANE Select: NM_005807
Type: single nucleotide variant
Location: chr1:186307260 (GRCh38)
Gene constraint: LOEUF 0.801 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 48.76
Residue 514: the 'disordered' region; the '59 x 8 aa repeats of k-x-p-x-p-t-t-x' region

Full PRG4 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

PRG4 p.Ala1246Val Uncertain significance ★★ ⚠ same condition
PRG4 p.Asp87Asn Uncertain significance ★★ ⚠ same condition
PRG4 p.Lys287Arg Uncertain significance ★★ ⚠ same condition
PRG4 p.Pro409Leu Uncertain significance ★★ ⚠ same condition
PRG4 p.Val1399Phe Uncertain significance ★★ ⚠ same condition
PRG4 p.Ala641Thr Likely benign ★★ same condition
PRG4 p.Glu403Lys Likely benign ★★ same condition
PRG4 p.Leu648= Likely benign ★★ 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/prg4-p-pro514arg (accessed [today's date]).

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