Is DKC1 p.Ser513Tyr (c.1538C>A) pathogenic?

DKC1 p.Ser513Tyr (c.1538C>A) is classified Uncertain significance in DKC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely benign (0.1445); Very rare (popmax 0.00406%, nfe); Associated with dyskeratosis congenita.

What condition is associated with DKC1 p.Ser513Tyr (c.1538C>A)?

DKC1 p.Ser513Tyr (c.1538C>A) is associated with dyskeratosis congenita (ClinVar).

How common is DKC1 p.Ser513Tyr (c.1538C>A) in the general population?

DKC1 p.Ser513Tyr (c.1538C>A) is very rare (popmax 0.00406%, nfe) (gnomAD).

How is Dyskeratosis congenita inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DKC1 p.Ser513Tyr (c.1538C>A)?

AlphaMissense predicts likely benign (score 0.1445) — an in-silico prediction, not a clinical call.

DKC1 p.Ser513Tyr

c.1538C>A · VCV4240877

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1445 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00406%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

dyskeratosis congenita

Computational evidence

Protein change
AlphaMissense	0.1445	likely benign
REVEL	0.393	indeterminate
SaProt	LLR -10.03	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 2.8, phastCons 0.96
Regional constraint	o/e 0.84	unconstrained · MANE · 1,637 bp · p 0.19 · regional, not allelic
Overall
CADD	20.6	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

Grpmax group 0.00406% European (non-Finnish) · 36/887,370 alleles

Filtering AF 0.00297% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00264%

Overall 0.003% 36/1,198,376 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.Ser513Tyr
Coding: c.1538C>A
MANE Select: NM_001363
Type: single nucleotide variant
Location: chrX:154776860 (GRCh38)
Structure: AlphaFold pLDDT 79.74 · 7 PDB
Residue 513: a modified residue (phosphoserine); the 'disordered' region; the 'nuclear and nucleolar localization' region

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

Disease context

dyskeratosis congenita — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Dyskeratosis congenita (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Adolescent, Adult, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

DKC1 p.Ala353Val Pathogenic ★★ ⚠ same condition
DKC1 p.Asn63Lys Pathogenic/Likely pathogenic ★★ ⚠ same condition
DKC1 p.Thr49Met Pathogenic ★★ ⚠ same condition
DKC1 p.Thr66Ala Pathogenic/Likely pathogenic ★★ ⚠ same condition
DKC1 c.1339-10T>G Uncertain significance ★★ same condition
DKC1 c.16+5G>A Uncertain significance ★★ same condition
DKC1 c.640+3G>A Uncertain significance ★★ same condition
DKC1 p.Ala162Thr 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-ser513tyr (accessed [today's date]).

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