Is PRKACA p.Glu209Asp (c.627G>T) pathogenic?

PRKACA p.Glu209Asp (c.627G>T) is classified Uncertain significance in PRKACA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-26). AlphaMissense: likely pathogenic (0.9975); Absent from gnomAD v4.1; Associated with cardioacrofacial dysplasia 1.

What condition is associated with PRKACA p.Glu209Asp (c.627G>T)?

PRKACA p.Glu209Asp (c.627G>T) is associated with cardioacrofacial dysplasia 1 (ClinVar).

How common is PRKACA p.Glu209Asp (c.627G>T) in the general population?

PRKACA p.Glu209Asp (c.627G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRKACA p.Glu209Asp (c.627G>T)?

AlphaMissense predicts likely pathogenic (score 0.9975) — an in-silico prediction, not a clinical call.

PRKACA p.Glu209Asp

c.627G>T · rs780953754 · VCV2435242

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9975 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

cardioacrofacial dysplasia 1

Computational evidence

Protein change
AlphaMissense	0.9975	likely pathogenic
REVEL	0.409	indeterminate
SaProt	LLR -13.22	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.99	phastCons 1
Regional constraint	o/e 0.39	unconstrained · MANE · 7,215 bp · p 3e-21 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRKACA
Protein: p.Glu209Asp
Coding: c.627G>T
MANE Select: NM_002730
dbSNP: rs780953754
Type: single nucleotide variant
Location: chr19:14097594 (GRCh38)
Gene constraint: LOEUF 0.338 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 95.92 · 54 PDB
Residue 209: the protein kinase domain; an α-helix

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

Disease context

cardioacrofacial dysplasia 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRKACA p.Gly137Arg Pathogenic/Likely pathogenic ★★ same condition
PRKACA p.Asn341Ser Uncertain significance ★★ ⚠ same condition
PRKACA c.47-322G>A Uncertain significance ★ same condition
PRKACA c.47-404C>T Conflicting classifications of pathogenicity ★ same condition
PRKACA p.Glu108Ala Uncertain significance ★ ⚠ same condition
PRKACA p.Gly201Ser Conflicting classifications of pathogenicity ★ ⚠ same condition
PRKACA p.Ile292Thr Uncertain significance ★ ⚠ same condition
PRKACA p.Leu75= 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/prkaca-p-glu209asp (accessed [today's date]).

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