Is DKC1 p.Arg19Gly (c.55C>G) pathogenic?

DKC1 p.Arg19Gly (c.55C>G) is classified Uncertain significance in DKC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-01). AlphaMissense: likely benign (0.081); Very rare (popmax 0.000112%, nfe).

How common is DKC1 p.Arg19Gly (c.55C>G) in the general population?

DKC1 p.Arg19Gly (c.55C>G) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about DKC1 p.Arg19Gly (c.55C>G)?

AlphaMissense predicts likely benign (score 0.081) — an in-silico prediction, not a clinical call.

DKC1 p.Arg19Gly

c.55C>G · rs782010351 · VCV1335800

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.081 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.081	likely benign
REVEL	0.421	indeterminate
SaProt	LLR -7.18	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.36	GERP 1.7, phastCons 0.031
Regional constraint	o/e 0.35	constrained · MANE · 4,035 bp · p 1.8e-12 · regional, not allelic
Overall
CADD	23.0	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 and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000112% European (non-Finnish) · 1/892,054 alleles

Overall 9.14e-05% 1/1,094,296 alleles · very rare

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: DKC1
Protein: p.Arg19Gly
Coding: c.55C>G
MANE Select: NM_001363
dbSNP: rs782010351
Type: single nucleotide variant
Location: chrX:154764937 (GRCh38)
Structure: AlphaFold pLDDT 79.74 · 7 PDB
Residue 19: the 'nucleolar localization' region

Full DKC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DKC1 p.Arg19Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
DKC1 p.Ala353Val Pathogenic ★★ ⚠ same type
DKC1 p.Asn63Lys Pathogenic/Likely pathogenic ★★ ⚠ same type
DKC1 p.Ile38Met Likely pathogenic ★★ ⚠ same type
DKC1 p.Thr49Met Pathogenic ★★ ⚠ same type
DKC1 p.Thr66Ala Pathogenic/Likely pathogenic ★★ ⚠ same type
DKC1 c.1339-10T>G Uncertain significance ★★ same type
DKC1 c.16+5G>A 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/dkc1-p-arg19gly (accessed [today's date]).

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