Is PRKDC p.Pro102Ser (c.304C>T) pathogenic?

PRKDC p.Pro102Ser (c.304C>T) is classified Uncertain significance in PRKDC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-01). AlphaMissense: likely benign (0.1146); Ultra-rare (popmax 0.0226%, mid).

How common is PRKDC p.Pro102Ser (c.304C>T) in the general population?

PRKDC p.Pro102Ser (c.304C>T) is ultra-rare (popmax 0.0226%, mid) (gnomAD).

What do computational predictors say about PRKDC p.Pro102Ser (c.304C>T)?

AlphaMissense predicts likely benign (score 0.1146) — an in-silico prediction, not a clinical call.

PRKDC p.Pro102Ser

c.304C>T · rs1462849968 · VCV1799243

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1146 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0226%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1146	likely benign
REVEL	0.216	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; 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 7.6	GERP 2, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 2,950 bp · p 0.46 · regional, not allelic
Overall
CADD	19.73	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

Grpmax group 0.0226% Middle Eastern · 1/4,418 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000189% 3/1,588,020 alleles · ultra-rare exomes 3/1,435,918 · genomes 0/152,102 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0226%	4,418
European (non-Finnish)	0.000173%	579,425

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.Pro102Ser
Coding: c.304C>T
MANE Select: NM_006904
dbSNP: rs1462849968
Type: single nucleotide variant
Location: chr8:47957191 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 (gnomAD)
Residue 102: an α-helix

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

Similar variants

PRKDC p.Pro102Ala Uncertain significance ★ ⚠ same residue
PRKDC p.Pro102His 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
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-pro102ser (accessed [today's date]).

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