Is PRKDC p.Phe1672Ser (c.5015T>C) pathogenic?

PRKDC p.Phe1672Ser (c.5015T>C) is classified Uncertain significance in PRKDC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-29). AlphaMissense: likely pathogenic (0.7862); No allele count reported in gnomAD v4.1 (AN 1,580,422).

How common is PRKDC p.Phe1672Ser (c.5015T>C) in the general population?

PRKDC p.Phe1672Ser (c.5015T>C) is no allele count reported in gnomAD v4.1 (AN 1,580,422) (gnomAD).

What do computational predictors say about PRKDC p.Phe1672Ser (c.5015T>C)?

AlphaMissense predicts likely pathogenic (score 0.7862) — an in-silico prediction, not a clinical call.

PRKDC p.Phe1672Ser

c.5015T>C · rs2551872549 · VCV1744781

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7862 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,580,422)

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.7862	likely pathogenic
REVEL	0.796	moderately pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; 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 11	phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 90 kb · p 0.028 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

No allele count reported in gnomAD v4.1 (AN 1,580,422). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PRKDC
Protein: p.Phe1672Ser
Coding: c.5015T>C
MANE Select: NM_006904
dbSNP: rs2551872549
Type: single nucleotide variant
Location: chr8:47881468 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 (gnomAD)
Residue 1672: an α-helix

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

Similar variants

PRKDC p.Phe1672Cys Uncertain significance ★ same residue
PRKDC p.Phe1672= 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

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-phe1672ser (accessed [today's date]).

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