Is DKC1 p.Glu206Lys (c.616G>A) pathogenic?

DKC1 p.Glu206Lys (c.616G>A) is classified Pathogenic in DKC1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-09-10). AlphaMissense: likely pathogenic (0.9515); Absent from gnomAD v4.1; Associated with cataracts, hearing impairment, nephrotic syndrome, and enterocolitis 1.

What condition is associated with DKC1 p.Glu206Lys (c.616G>A)?

DKC1 p.Glu206Lys (c.616G>A) is associated with cataracts, hearing impairment, nephrotic syndrome, and enterocolitis 1 (ClinVar).

How common is DKC1 p.Glu206Lys (c.616G>A) in the general population?

DKC1 p.Glu206Lys (c.616G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DKC1 p.Glu206Lys (c.616G>A)?

AlphaMissense predicts likely pathogenic (score 0.9515) — an in-silico prediction, not a clinical call.

DKC1 p.Glu206Lys

c.616G>A · rs2523685088 · VCV2506511

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9515 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cataracts, hearing impairment, nephrotic syndrome, and enterocolitis 1

Computational evidence

Protein change
AlphaMissense	0.9515	likely pathogenic ✓ concordant with ClinVar
REVEL	0.723	pathogenic-leaning
SaProt	LLR -14.84	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 4.2, phastCons 1
Regional constraint	o/e 0.29	constrained · MANE · 8,165 bp · p 2.1e-24 · regional, not allelic
Overall
CADD	29.5	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.Glu206Lys
Coding: c.616G>A
MANE Select: NM_001363
dbSNP: rs2523685088
Type: single nucleotide variant
Location: chrX:154767358 (GRCh38)
Structure: AlphaFold pLDDT 79.74 · 7 PDB
Residue 206: a UniProt-annotated variant site (in chine1; likely pathogenic; decreased rrna pseudouridine synthesis in peripheral blood cells from a severely affected female; unable to fully rescue developmental defects in dkc1-null zebrafish morphants; does not affect interaction with nop10); a β-strand

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

Disease context

cataracts, hearing impairment, nephrotic syndrome, and enterocolitis 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DKC1 p.Gln414Glu Uncertain significance ★★ ⚠ same condition
DKC1 p.Lys505Asn Uncertain significance ★★ ⚠ same condition
DKC1 p.Met301Val Uncertain significance ★★ ⚠ same condition
DKC1 p.Ser451Arg Uncertain significance ★★ ⚠ same condition
DKC1 p.Asp85Asn Conflicting classifications of pathogenicity ★ ⚠ same condition
DKC1 p.Glu450Asp Conflicting classifications of pathogenicity ★ ⚠ same condition
DKC1 p.Ile466Val Uncertain significance ★ ⚠ same condition
DKC1 p.Thr118Pro Uncertain significance ★ ⚠ same condition

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-glu206lys (accessed [today's date]).

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