Is DKC1 p.Arg449Gly (c.1345C>G) pathogenic?

DKC1 p.Arg449Gly (c.1345C>G) is classified Pathogenic in DKC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2015-12-17). AlphaMissense: likely benign (0.338); Absent from gnomAD v4.1.

How common is DKC1 p.Arg449Gly (c.1345C>G) in the general population?

DKC1 p.Arg449Gly (c.1345C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DKC1 p.Arg449Gly (c.1345C>G)?

AlphaMissense predicts likely benign (score 0.338) — an in-silico prediction, not a clinical call.

DKC1 p.Arg449Gly

c.1345C>G · rs878853071 · VCV235576

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.338 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.338	likely benign ⚠ discordant with ClinVar
REVEL	0.545	indeterminate
SaProt	LLR -7.27	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 2.3	GERP 3, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 1,637 bp · p 0.19 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: DKC1
Protein: p.Arg449Gly
Coding: c.1345C>G
MANE Select: NM_001363
dbSNP: rs878853071
Type: single nucleotide variant
Location: chrX:154776193 (GRCh38)
Structure: AlphaFold pLDDT 79.74 · 7 PDB
Residue 449: the 'disordered' region; the 'nuclear and nucleolar localization' region

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

Similar variants

DKC1 p.Arg449Gln Uncertain significance ★ ⚠ same residue
DKC1 p.Arg449Pro Uncertain significance ★ ⚠ 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

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-arg449gly (accessed [today's date]).

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