Is PRG4 p.Pro688Ser (c.2062C>T) pathogenic?

PRG4 p.Pro688Ser (c.2062C>T) is classified Uncertain significance in PRG4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-13). AlphaMissense: likely benign (0.1459); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PRG4 p.Pro688Ser (c.2062C>T)?

PRG4 p.Pro688Ser (c.2062C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PRG4 p.Pro688Ser (c.2062C>T) in the general population?

PRG4 p.Pro688Ser (c.2062C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRG4 p.Pro688Ser (c.2062C>T)?

AlphaMissense predicts likely benign (score 0.1459) — an in-silico prediction, not a clinical call.

PRG4 p.Pro688Ser

c.2062C>T · rs748829259 · VCV3218621

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1459 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1459	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -9.84	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 -10	GERP -0.98
Regional constraint	o/e 0.93	unconstrained · MANE · 6,664 bp · p 0.015 · regional, not allelic
Overall
CADD	0.468	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

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: PRG4
Protein: p.Pro688Ser
Coding: c.2062C>T
MANE Select: NM_005807
dbSNP: rs748829259
Type: single nucleotide variant
Location: chr1:186307781 (GRCh38)
Gene constraint: LOEUF 0.801 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 48.76
Residue 688: 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-pro688ser (accessed [today's date]).

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