Is PRKCQ p.Pro55Ser (c.163C>T) pathogenic?

PRKCQ p.Pro55Ser (c.163C>T) is classified Uncertain significance in PRKCQ (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-11). AlphaMissense: likely benign (0.1026); Very rare (popmax 0.00133%, afr).

How common is PRKCQ p.Pro55Ser (c.163C>T) in the general population?

PRKCQ p.Pro55Ser (c.163C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about PRKCQ p.Pro55Ser (c.163C>T)?

AlphaMissense predicts likely benign (score 0.1026) — an in-silico prediction, not a clinical call.

PRKCQ p.Pro55Ser

c.163C>T · rs1838455992 · VCV2610723

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1026 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1026	likely benign
REVEL	0.095	moderately benign-leaning
SaProt	LLR -6.20	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.5, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 87 kb · p 8.3e-14 · regional, not allelic
Overall
CADD	22.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00133% African / African-American · 1/75,014 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00109% 16/1,461,862 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,014
European (non-Finnish)	0.00127%	78,668

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: PRKCQ
Protein: p.Pro55Ser
Coding: c.163C>T
MANE Select: NM_006257
dbSNP: rs1838455992
Type: single nucleotide variant
Location: chr10:6511150 (GRCh38)
Gene constraint: LOEUF 0.571 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.20 · 8 PDB
Residue 55: the c2 domain

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

Similar variants

PRKCQ p.Ile214Val Benign ★★ same type
PRKCQ p.Ser479Cys Benign ★★ ⚠ same type
PRKCQ p.Thr442= Benign ★★ same type
PRKCQ p.Ala152Thr Uncertain significance ★ ⚠ same type
PRKCQ p.Ala407Thr Uncertain significance ★ ⚠ same type
PRKCQ p.Ala410Ser Uncertain significance ★ ⚠ same type
PRKCQ p.Ala521Thr Uncertain significance ★ ⚠ same type
PRKCQ p.Ala521Val 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/prkcq-p-pro55ser (accessed [today's date]).

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