Is PRKD1 p.Pro90Ser (c.268C>T) pathogenic?

PRKD1 p.Pro90Ser (c.268C>T) is classified Likely benign in PRKD1 (ClinVar, Single submitter, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely pathogenic (0.9612); Rare (popmax 0.13%, amr).

How common is PRKD1 p.Pro90Ser (c.268C>T) in the general population?

PRKD1 p.Pro90Ser (c.268C>T) is rare (popmax 0.13%, amr) (gnomAD).

What do computational predictors say about PRKD1 p.Pro90Ser (c.268C>T)?

AlphaMissense predicts likely pathogenic (score 0.9612) — an in-silico prediction, not a clinical call.

PRKD1 p.Pro90Ser

c.268C>T · rs45458201 · VCV734679

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9612 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.13%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9612	likely pathogenic
REVEL	0.828	moderately pathogenic-leaning
SaProt	LLR -9.98	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 4.1, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 264 kb · p 0.094 · regional, not allelic
Overall
CADD	26.5	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

Grpmax group 0.13% Admixed American · 78/59,824 alleles

Filtering AF 0.107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0984%

Overall 0.00484% 78/1,612,458 alleles · rare exomes 75/1,460,490 · genomes 3/151,968 · joint denominator

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: PRKD1
Protein: p.Pro90Ser
Coding: c.268C>T
MANE Select: NM_002742
dbSNP: rs45458201
Type: single nucleotide variant
Location: chr14:29725671 (GRCh38)
Gene constraint: LOEUF 0.762 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.99

Full PRKD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRKD1 p.Pro90Ala Uncertain significance ★ ⚠ same residue
PRKD1 p.Ala529Thr Uncertain significance ★★ ⚠ same type
PRKD1 p.Arg201Trp Uncertain significance ★★ same type
PRKD1 p.Arg203Lys Uncertain significance ★★ ⚠ same type
PRKD1 p.Arg740Gln Uncertain significance ★★ ⚠ same type
PRKD1 p.Asn498Ser Uncertain significance ★★ ⚠ same type
PRKD1 p.Gln115His Uncertain significance ★★ ⚠ same type
PRKD1 p.Gly486Arg 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/prkd1-p-pro90ser (accessed [today's date]).

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