Is PRG4 p.Pro1111Ser (c.3331C>T) pathogenic?

PRG4 p.Pro1111Ser (c.3331C>T) is classified Likely benign in PRG4 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-09-17). AlphaMissense: likely benign (0.1571); Rare (popmax 0.628%, sas).

How common is PRG4 p.Pro1111Ser (c.3331C>T) in the general population?

PRG4 p.Pro1111Ser (c.3331C>T) is rare (popmax 0.628%, sas) (gnomAD).

What do computational predictors say about PRG4 p.Pro1111Ser (c.3331C>T)?

AlphaMissense predicts likely benign (score 0.1571) — an in-silico prediction, not a clinical call.

PRG4 p.Pro1111Ser

c.3331C>T · rs201472102 · VCV3034267

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1571 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.628%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1571	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -7.09	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 2	GERP 0.44, phastCons 0.95
Regional constraint	o/e 0.93	unconstrained · MANE · 6,664 bp · p 0.015 · regional, not allelic
Overall
CADD	14.08	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 0.628% South Asian · 572/91,052 alleles

Filtering AF 0.586% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.569%

Overall 0.0379% 611/1,613,818 alleles · rare exomes 582/1,461,560 · genomes 29/152,258 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.628%	159
Remaining individualsnot grpmax-eligible	0.0416%	2,403
Middle Eastern	0.033%	3,030
African / African-American	0.00533%	18,754
Admixed American	0.00333%	30,002
European (non-Finnish)	0.000424%	235,965

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.Pro1111Ser
Coding: c.3331C>T
MANE Select: NM_005807
dbSNP: rs201472102
Type: single nucleotide variant
Location: chr1:186309050 (GRCh38)
Gene constraint: LOEUF 0.801 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 48.76

Full PRG4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRG4 p.Arg1166Ter Pathogenic/Likely pathogenic ★★ same type
PRG4 p.Ser1355Ter Pathogenic/Likely pathogenic ★★ same type
PRG4 p.Ala1246Val Uncertain significance ★★ ⚠ same type
PRG4 p.Asp87Asn Uncertain significance ★★ ⚠ same type
PRG4 p.Lys287Arg Uncertain significance ★★ ⚠ same type
PRG4 p.Pro409Leu Uncertain significance ★★ ⚠ same type
PRG4 p.Val1399Phe Uncertain significance ★★ ⚠ same type
PRG4 c.-30-30T>A 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/prg4-p-pro1111ser (accessed [today's date]).

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