Is PRKDC p.Ser3779Phe (c.11336C>T) pathogenic?

PRKDC p.Ser3779Phe (c.11336C>T) is classified Likely benign in PRKDC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-19). AlphaMissense: likely benign (0.1966); Absent from gnomAD v4.1; Associated with PRKDC-related disorder.

What condition is associated with PRKDC p.Ser3779Phe (c.11336C>T)?

PRKDC p.Ser3779Phe (c.11336C>T) is associated with PRKDC-related disorder (ClinVar).

How common is PRKDC p.Ser3779Phe (c.11336C>T) in the general population?

PRKDC p.Ser3779Phe (c.11336C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRKDC p.Ser3779Phe (c.11336C>T)?

AlphaMissense predicts likely benign (score 0.1966) — an in-silico prediction, not a clinical call.

PRKDC p.Ser3779Phe

c.11336C>T · rs2551860399 · VCV1728929

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1966 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

PRKDC-related disorder

Computational evidence

Protein change
AlphaMissense	0.1966	likely benign
REVEL	0.532	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 25 kb · p 7.5e-15 · regional, not allelic
Overall
CADD	22.0	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

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: PRKDC
Protein: p.Ser3779Phe
Coding: c.11336C>T
MANE Select: NM_006904
dbSNP: rs2551860399
Type: single nucleotide variant
Location: chr8:47782438 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 (gnomAD)
Residue 3779: an α-helix; the pi3k/pi4k catalytic domain

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

Disease context

PRKDC-related disorder

Similar variants

PRKDC p.Ser3779= Benign/Likely benign ★★ same residue
PRKDC p.Arg3425Leu Uncertain significance ★★ same condition
PRKDC p.Gly1314Cys Benign/Likely benign ★★ same condition
PRKDC p.Lys3075= Likely benign ★★ same condition
PRKDC p.Tyr2775= Likely benign ★★ same condition
PRKDC p.Val1596= Likely benign ★★ same condition
PRKDC p.Val3793Ala Benign/Likely benign ★★ same condition
PRKDC p.Phe2300Leu Conflicting classifications of pathogenicity ★ ⚠ 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/prkdc-p-ser3779phe (accessed [today's date]).

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