Is PRKACA p.Pro208= (c.624T>G) pathogenic?

PRKACA p.Pro208= (c.624T>G) is classified Likely benign in PRKACA (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-29). Very rare (popmax 0.00238%, nfe).

How common is PRKACA p.Pro208= (c.624T>G) in the general population?

PRKACA p.Pro208= (c.624T>G) is very rare (popmax 0.00238%, nfe) (gnomAD).

PRKACA p.Pro208=

c.624T>G · rs1599336336 · VCV737730

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00238%, 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 -11
Overall
CADD	0.24	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00238% European (non-Finnish) · 28/1,178,738 alleles

Filtering AF 0.00165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00233% 34/1,460,176 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,520
Remaining individualsnot grpmax-eligible	0.0032%	31,215
European (non-Finnish)grpmax	0.00238%	42,098
South Asian	0.0022%	45,494
African / African-American	0.00133%	74,980

Ashkenazi Jewish 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: PRKACA
Protein: p.Pro208=
Coding: c.624T>G
MANE Select: NM_002730
dbSNP: rs1599336336
Type: single nucleotide variant
Location: chr19:14097597 (GRCh38)
Gene constraint: LOEUF 0.338 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 95.92 · 54 PDB
Residue 208: the protein kinase domain; an α-helix

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

Similar variants

PRKACA p.Gly137Arg Pathogenic/Likely pathogenic ★★ same type
PRKACA p.Arg271Trp Uncertain significance ★★ ⚠ same type
PRKACA p.Asn341Ser Uncertain significance ★★ ⚠ same type
PRKACA p.Gly67Arg Uncertain significance ★★ ⚠ same type
PRKACA c.109-6C>T Benign/Likely benign ★★ same type
PRKACA c.47-418C>T Benign/Likely benign ★★ same type
PRKACA p.Arg281= Benign ★★ same type
PRKACA p.Gly127= 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/prkaca-p-pro208 (accessed [today's date]).

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