Is DKC1 p.Ala487= (c.1461C>T) pathogenic?

DKC1 p.Ala487= (c.1461C>T) is classified Benign/Likely benign in DKC1 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 12.1%, afr) — too common for a highly-penetrant pathogenic allele; Associated with dyskeratosis congenita.

What condition is associated with DKC1 p.Ala487= (c.1461C>T)?

DKC1 p.Ala487= (c.1461C>T) is associated with dyskeratosis congenita (ClinVar).

How is Dyskeratosis congenita inherited?

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

DKC1 p.Ala487=

Q: How common is DKC1 p.Ala487= (c.1461C>T) in the general population?

DKC1 p.Ala487= (c.1461C>T) is common (popmax 12.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1461C>T · rs1127051 · VCV128896

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 12.1%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

dyskeratosis congenita

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.9	GERP -4.8
Overall
CADD	2.026	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 12.1% African / African-American · 6,884/56,748 alleles

Filtering AF 11.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.8%

Overall 6.21% 74,104/1,193,942 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	12.1%	8
European (non-Finnish)	6.59%	15
Remaining individualsnot grpmax-eligible	5.63%	18
East Asian	4.57%	22
Finnishnot grpmax-eligible	4.54%	22
Admixed American	3.76%	27
Ashkenazi Jewishnot grpmax-eligible	2.84%	35
Middle Eastern	1.37%	73
South Asian	0.551%	182

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.Ala487=
Coding: c.1461C>T
MANE Select: NM_001363
dbSNP: rs1127051
Type: single nucleotide variant
Location: chrX:154776309 (GRCh38)
Structure: AlphaFold pLDDT 79.74 · 7 PDB
Residue 487: 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-ala487 (accessed [today's date]).

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