Is PRR12 p.Pro650Ser (c.1948C>T) pathogenic?

PRR12 p.Pro650Ser (c.1948C>T) is classified Benign in PRR12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-01). AlphaMissense: ambiguous (0.412); Rare (popmax 0.216%, mid).

How common is PRR12 p.Pro650Ser (c.1948C>T) in the general population?

PRR12 p.Pro650Ser (c.1948C>T) is rare (popmax 0.216%, mid) (gnomAD).

What do computational predictors say about PRR12 p.Pro650Ser (c.1948C>T)?

AlphaMissense predicts ambiguous (score 0.412) — an in-silico prediction, not a clinical call.

PRR12 p.Pro650Ser

c.1948C>T · VCV3770672

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.412 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.216%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.412	ambiguous
REVEL	0.085	moderately benign-leaning
SaProt	LLR -6.07	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.5	GERP 1.5, phastCons 1
Regional constraint	o/e 1.22	unconstrained · MANE · 1,459 bp · p 1.1e-08 · regional, not allelic
Overall
CADD	21.5	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 0.216% Middle Eastern · 13/6,032 alleles

Filtering AF 0.127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.101%

Overall 0.0225% 362/1,611,444 alleles · rare exomes 304/1,459,132 · genomes 58/152,312 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.216%	464
Finnishnot grpmax-eligible	0.154%	648
Admixed American	0.0685%	1,460
Remaining individualsnot grpmax-eligible	0.0353%	2,836
European (non-Finnish)	0.0153%	6,517
South Asian	0.00879%	11,374
African / African-American	0.00133%	75,046

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.Pro650Ser
Coding: c.1948C>T
MANE Select: NM_020719
Type: single nucleotide variant
Location: chr19:49596283 (GRCh38)
Gene constraint: LOEUF 0.18 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.84
Residue 650: the 'disordered' region; a UniProt-annotated variant site (in noc1)

Full PRR12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRR12 p.Pro650Ala Uncertain significance ★ ⚠ same residue
PRR12 p.Arg1169Trp Likely pathogenic ★★ ⚠ same type
PRR12 p.Arg1320Ter Pathogenic ★★ same type
PRR12 p.Gln264Ter Pathogenic ★★ same type
PRR12 p.Gln919Ter Pathogenic ★★ same type
PRR12 p.Glu640Ter Pathogenic ★★ same type
PRR12 p.Ala1190Ser Uncertain significance ★★ ⚠ same type
PRR12 p.Ala82Gly Uncertain significance ★★ ⚠ 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/prr12-p-pro650ser (accessed [today's date]).

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