Is PRR12 p.Pro1111= (c.3333C>T) pathogenic?

PRR12 p.Pro1111= (c.3333C>T) is classified Likely benign in PRR12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). Very rare (popmax 0.00268%, afr); Associated with Inborn genetic diseases.

What condition is associated with PRR12 p.Pro1111= (c.3333C>T)?

PRR12 p.Pro1111= (c.3333C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PRR12 p.Pro1111= (c.3333C>T) in the general population?

PRR12 p.Pro1111= (c.3333C>T) is very rare (popmax 0.00268%, afr) (gnomAD).

PRR12 p.Pro1111=

c.3333C>T · VCV4145116

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00268%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -16	GERP -2.6
Overall
CADD	0.503	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00268% African / African-American · 2/74,732 alleles

Filtering AF 0.000444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000498% 8/1,605,266 alleles · very rare exomes 7/1,453,114 · genomes 1/152,152 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00268%	37,366
South Asian	0.00223%	44,765
Remaining individualsnot grpmax-eligible	0.00161%	62,128
European (non-Finnish)	0.000255%	392,386

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: PRR12
Protein: p.Pro1111=
Coding: c.3333C>T
MANE Select: NM_020719
Type: single nucleotide variant
Location: chr19:49597668 (GRCh38)
Gene constraint: LOEUF 0.18 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.84
Residue 1111: a UniProt-annotated variant site (in noc1)

Full PRR12 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

PRR12 p.Ala1190Ser Uncertain significance ★★ ⚠ same condition
PRR12 p.Ala82Gly Uncertain significance ★★ ⚠ same condition
PRR12 p.Arg1755Gln Uncertain significance ★★ ⚠ same condition
PRR12 p.Asp1109Tyr Uncertain significance ★★ ⚠ same condition
PRR12 p.Glu1100Lys Uncertain significance ★★ ⚠ same condition
PRR12 p.Glu943Ala Uncertain significance ★★ ⚠ same condition
PRR12 p.Gly1566Ser Uncertain significance ★★ ⚠ same condition
PRR12 p.Gly963Ser 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/prr12-p-pro1111 (accessed [today's date]).

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