Is DKC1 p.Ala73= (c.219A>G) pathogenic?

DKC1 p.Ala73= (c.219A>G) is classified Likely benign in DKC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-27). Ultra-rare (popmax 0.0457%, mid); Associated with dyskeratosis congenita.

What condition is associated with DKC1 p.Ala73= (c.219A>G)?

DKC1 p.Ala73= (c.219A>G) is associated with dyskeratosis congenita (ClinVar).

How common is DKC1 p.Ala73= (c.219A>G) in the general population?

DKC1 p.Ala73= (c.219A>G) is ultra-rare (popmax 0.0457%, mid) (gnomAD).

How is Dyskeratosis congenita inherited?

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

DKC1 p.Ala73=

c.219A>G · rs1036932842 · VCV2972681

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0457%, mid)

Conditions

dyskeratosis congenita

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.024	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.65	GERP -2.8, phastCons 1
Overall
CADD	7.403	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0457% Middle Eastern · 2/4,372 alleles

Filtering AF 0.00809% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00339%

Overall 0.000496% 6/1,208,496 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0457%	2,186
African / African-American	0.00175%	57,135
European (non-Finnish)	0.000336%	297,889

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.Ala73=
Coding: c.219A>G
MANE Select: NM_001363
dbSNP: rs1036932842
Type: single nucleotide variant
Location: chrX:154765954 (GRCh38)
Structure: AlphaFold pLDDT 79.74 · 7 PDB

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-ala73 (accessed [today's date]).

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