Is DKC1 p.Ala2Val (c.5C>T) pathogenic?

DKC1 p.Ala2Val (c.5C>T) is classified Conflicting classifications of pathogenicity in DKC1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2023-04-28). AlphaMissense: ambiguous (0.3409); Absent from gnomAD v4.1; Associated with dyskeratosis congenita.

What condition is associated with DKC1 p.Ala2Val (c.5C>T)?

DKC1 p.Ala2Val (c.5C>T) is associated with dyskeratosis congenita, dyskeratosis congenita, X-linked (ClinVar).

How common is DKC1 p.Ala2Val (c.5C>T) in the general population?

DKC1 p.Ala2Val (c.5C>T) is absent from gnomAD v4.1 (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.Ala2Val (c.5C>T)?

AlphaMissense predicts ambiguous (score 0.3409) — an in-silico prediction, not a clinical call.

DKC1 p.Ala2Val

c.5C>T · rs121912303 · VCV38951

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

ambiguous

0.3409 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,182,113)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

dyskeratosis congenita

Computational evidence

Protein change
AlphaMissense	0.3409	ambiguous
REVEL	0.663	pathogenic-leaning
SaProt	LLR -9.29	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.1	GERP 3.2, phastCons 1
Regional constraint	o/e 0.35	constrained · MANE · 4,035 bp · p 1.8e-12 · regional, not allelic
Overall
CADD	26.4	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

No allele count reported in gnomAD v4.1 (AN 1,182,113). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DKC1
Protein: p.Ala2Val
Coding: c.5C>T
MANE Select: NM_001363
dbSNP: rs121912303
Type: single nucleotide variant
Location: chrX:154762970 (GRCh38)
Structure: AlphaFold pLDDT 79.74 · 7 PDB
Residue 2: a UniProt-annotated variant site (in dkcx); the 'nucleolar localization' region; a modified residue (n-acetylalanine)

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

Also linked: dyskeratosis congenita, X-linked

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.Ala2del Pathogenic ★ same residue
DKC1 p.Ala353Val Pathogenic ★★ ⚠ same condition
DKC1 p.Asn63Lys Pathogenic/Likely pathogenic ★★ ⚠ same condition
DKC1 p.Ile38Met 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

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-ala2val (accessed [today's date]).

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