Is PRKDC p.Pro2604Ser (c.7810C>T) pathogenic?

PRKDC p.Pro2604Ser (c.7810C>T) is classified Uncertain significance in PRKDC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-30). AlphaMissense: likely pathogenic (0.789); Very rare (popmax 0.00111%, sas).

How common is PRKDC p.Pro2604Ser (c.7810C>T) in the general population?

PRKDC p.Pro2604Ser (c.7810C>T) is very rare (popmax 0.00111%, sas) (gnomAD).

What do computational predictors say about PRKDC p.Pro2604Ser (c.7810C>T)?

AlphaMissense predicts likely pathogenic (score 0.789) — an in-silico prediction, not a clinical call.

PRKDC p.Pro2604Ser

c.7810C>T · rs2551867352 · VCV1760742

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.789 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00111%, sas)

Computational evidence

Protein change
AlphaMissense	0.789	likely pathogenic
REVEL	0.337	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 63 kb · p 0.0014 · regional, not allelic
Overall
CADD	25.4	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 0.00111% South Asian · 1/90,384 alleles

Overall 6.21e-05% 1/1,610,784 alleles · very rare exomes 1/1,458,516 · genomes 0/152,268 · 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.Pro2604Ser
Coding: c.7810C>T
MANE Select: NM_006904
dbSNP: rs2551867352
Type: single nucleotide variant
Location: chr8:47836479 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 (gnomAD)
Residue 2604: the 'kip-binding' region

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

Similar variants

PRKDC p.Pro2604= Conflicting classifications of pathogenicity ★ same residue
PRKDC p.Pro2604Ala Uncertain significance ★ same residue
PRKDC p.Pro2604Leu Uncertain significance ★ 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

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-pro2604ser (accessed [today's date]).

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