Is PRKDC p.Pro1469Ser (c.4405C>T) pathogenic?

PRKDC p.Pro1469Ser (c.4405C>T) is classified Uncertain significance in PRKDC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-13). AlphaMissense: likely benign (0.1041); No allele count reported in gnomAD v4.1 (AN 1,557,518).

How common is PRKDC p.Pro1469Ser (c.4405C>T) in the general population?

PRKDC p.Pro1469Ser (c.4405C>T) is no allele count reported in gnomAD v4.1 (AN 1,557,518) (gnomAD).

What do computational predictors say about PRKDC p.Pro1469Ser (c.4405C>T)?

AlphaMissense predicts likely benign (score 0.1041) — an in-silico prediction, not a clinical call.

PRKDC p.Pro1469Ser

c.4405C>T · rs2551873554 · VCV2453167

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1041 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,557,518)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1041	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	phastCons 0.99
Regional constraint	o/e 0.95	unconstrained · MANE · 90 kb · p 0.028 · regional, not allelic
Overall
CADD	12.33	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 is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,557,518). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PRKDC
Protein: p.Pro1469Ser
Coding: c.4405C>T
MANE Select: NM_006904
dbSNP: rs2551873554
Type: single nucleotide variant
Location: chr8:47888526 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 (gnomAD)

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

Similar variants

PRKDC p.Pro1469Ala Uncertain significance ★ ⚠ same residue
PRKDC p.Pro1469= Likely benign ★ same residue
PRKDC c.2259+6C>T Uncertain significance ★★ same type
PRKDC c.3464+4G>A Uncertain significance ★★ same type
PRKDC c.5235+6T>C Uncertain significance ★★ same type
PRKDC c.5919+5G>A Uncertain significance ★★ same type
PRKDC p.Ala1008Val Uncertain significance ★★ ⚠ same type
PRKDC p.Ala1103Val 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/prkdc-p-pro1469ser (accessed [today's date]).

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