Is PRKAR1B p.Ser75= (c.225G>A) pathogenic?

PRKAR1B p.Ser75= (c.225G>A) is classified Likely benign in PRKAR1B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-03). Very rare (popmax 0.000848%, nfe).

How common is PRKAR1B p.Ser75= (c.225G>A) in the general population?

PRKAR1B p.Ser75= (c.225G>A) is very rare (popmax 0.000848%, nfe) (gnomAD).

PRKAR1B p.Ser75=

c.225G>A · VCV4894903

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000848%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.9	GERP -3.7
Overall
CADD	0.673	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000848% European (non-Finnish) · 10/1,179,918 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000682% 11/1,613,712 alleles · very rare exomes 11/1,461,452 · genomes 0/152,260 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)grpmax	0.000848%	117,992

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PRKAR1B
Protein: p.Ser75=
Coding: c.225G>A
MANE Select: NM_001164760
Type: single nucleotide variant
Location: chr7:680679 (GRCh38)
Gene constraint: LOEUF 0.686 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.24 · 3 PDB
Residue 75: the 'dimerization and phosphorylation' region; the 'disordered' region

Full PRKAR1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRKAR1B p.Arg335Trp Pathogenic/Likely pathogenic ★★ same type
DNAAF5 p.Asp87Tyr Uncertain significance ★★ ⚠ same type
DNAAF5 p.Cys138Gly Uncertain significance ★★ ⚠ same type
DNAAF5 p.Glu8Ala Uncertain significance ★★ ⚠ same type
DNAAF5 p.Gly150Arg Uncertain significance ★★ ⚠ same type
DNAAF5 p.Val6Ala Uncertain significance ★★ ⚠ same type
PRKAR1B p.Ala204Val Uncertain significance ★★ ⚠ same type
PRKAR1B p.Ala6Thr 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/prkar1b-p-ser75 (accessed [today's date]).

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