Is PRKAR1A p.Ser3Phe (c.8C>T) pathogenic?

PRKAR1A p.Ser3Phe (c.8C>T) is classified Uncertain significance in PRKAR1A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-24). AlphaMissense: likely benign (0.1349); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with PRKAR1A p.Ser3Phe (c.8C>T)?

PRKAR1A p.Ser3Phe (c.8C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is PRKAR1A p.Ser3Phe (c.8C>T) in the general population?

PRKAR1A p.Ser3Phe (c.8C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRKAR1A p.Ser3Phe (c.8C>T)?

AlphaMissense predicts likely benign (score 0.1349) — an in-silico prediction, not a clinical call.

PRKAR1A p.Ser3Phe

c.8C>T · rs752643409 · VCV3222779

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1349 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1349	likely benign
REVEL	0.38	indeterminate
SaProt	LLR -10.04	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 1, phastCons 0.5
Regional constraint	o/e 0.93	unconstrained · MANE · 7,453 bp · p 0.48 · regional, not allelic
Overall
CADD	22.6	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

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: PRKAR1A
Protein: p.Ser3Phe
Coding: c.8C>T
MANE Select: NM_002734
dbSNP: rs752643409
Type: single nucleotide variant
Location: chr17:68515407 (GRCh38)
Gene constraint: LOEUF 0.158 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 87.95 · 3 PDB
Residue 3: the 'dimerization and phosphorylation' region; a modified residue (phosphoserine)

Full PRKAR1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRKAR1A p.Ser3Pro Uncertain significance ★ ⚠ same residue
PRKAR1A c.502+1G>A Pathogenic/Likely pathogenic ★★ same condition
PRKAR1A c.891+3A>G Likely pathogenic ★★ same condition
PRKAR1A c.892-2A>G Pathogenic/Likely pathogenic ★★ same condition
PRKAR1A p.Arg16Ter Pathogenic ★★ same condition
PRKAR1A p.Arg97Ter Pathogenic ★★ same condition
PRKAR1A p.Met1Val Pathogenic ★★ same condition
PRKAR1A p.Trp190Ter Pathogenic/Likely pathogenic ★★ 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/prkar1a-p-ser3phe (accessed [today's date]).

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