Is PRKDC p.Arg2000Ser (c.6000A>C) pathogenic?

PRKDC p.Arg2000Ser (c.6000A>C) is classified Uncertain significance in PRKDC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-18). AlphaMissense: likely pathogenic (0.8503); Absent from gnomAD v4.1.

How common is PRKDC p.Arg2000Ser (c.6000A>C) in the general population?

PRKDC p.Arg2000Ser (c.6000A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRKDC p.Arg2000Ser (c.6000A>C)?

AlphaMissense predicts likely pathogenic (score 0.8503) — an in-silico prediction, not a clinical call.

PRKDC p.Arg2000Ser

c.6000A>C · rs2551870433 · VCV2453255

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8503 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.8503	likely pathogenic · top 9% in PRKDC
REVEL	0.253	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense calls this damaging; REVEL does not; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.93	GERP -1.4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 63 kb · p 0.0014 · regional, not allelic
Overall
CADD	21.5	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.Arg2000Ser
Coding: c.6000A>C
MANE Select: NM_006904
dbSNP: rs2551870433
Type: single nucleotide variant
Location: chr8:47860957 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 (gnomAD)
Residue 2000: an α-helix

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

Similar variants

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
PRKDC p.Ala1130Thr 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-arg2000ser (accessed [today's date]).

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