Is PRKDC p.Val569Ala (c.1706T>C) pathogenic?

PRKDC p.Val569Ala (c.1706T>C) is classified Uncertain significance in PRKDC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-04). AlphaMissense: ambiguous (0.5114); Very rare (popmax 6.3e-05%).

How common is PRKDC p.Val569Ala (c.1706T>C) in the general population?

PRKDC p.Val569Ala (c.1706T>C) is very rare (popmax 6.3e-05%) (gnomAD).

What do computational predictors say about PRKDC p.Val569Ala (c.1706T>C)?

AlphaMissense predicts ambiguous (score 0.5114) — an in-silico prediction, not a clinical call.

PRKDC p.Val569Ala

c.1706T>C · rs2551879029 · VCV1778461

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5114 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.3e-05%)

Computational evidence

Protein change
AlphaMissense	0.5114	ambiguous
REVEL	0.171	moderately benign-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 90 kb · p 0.028 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.3e-05%

Overall 6.3e-05% 1/1,587,204 alleles · very rare exomes 1/1,434,826 · genomes 0/152,378 · 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: PRKDC
Protein: p.Val569Ala
Coding: c.1706T>C
MANE Select: NM_006904
dbSNP: rs2551879029
Type: single nucleotide variant
Location: chr8:47933090 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 (gnomAD)
Residue 569: an α-helix

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

Similar variants

PRKDC p.Val569= 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
PRKDC p.Ala1130Ser 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-val569ala (accessed [today's date]).

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