Is DKC1 p.Val431= (c.1293G>A) pathogenic?

DKC1 p.Val431= (c.1293G>A) is classified Likely benign in DKC1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-15). Rare (popmax 0.19%, afr); Associated with dyskeratosis congenita.

What condition is associated with DKC1 p.Val431= (c.1293G>A)?

DKC1 p.Val431= (c.1293G>A) is associated with dyskeratosis congenita, DKC1-related disorder (ClinVar).

How common is DKC1 p.Val431= (c.1293G>A) in the general population?

DKC1 p.Val431= (c.1293G>A) is rare (popmax 0.19%, afr) (gnomAD).

How is Dyskeratosis congenita inherited?

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

DKC1 p.Val431=

c.1293G>A · rs138065506 · VCV697360

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.19%, afr)

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 -1.1	GERP -7.5
Overall
CADD	0.807	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.19% African / African-American · 109/57,398 alleles

Filtering AF 0.161% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.15%

Overall 0.00942% 114/1,210,751 alleles · rare exomes 51/1,098,020 · genomes 63/112,731 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.19%	527
Remaining individualsnot grpmax-eligible	0.0084%	11,899
South Asian	0.00176%	56,919

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.Val431=
Coding: c.1293G>A
MANE Select: NM_001363
dbSNP: rs138065506
Type: single nucleotide variant
Location: chrX:154775228 (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

Also linked: DKC1-related disorder

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.Val431_Glu440del Uncertain significance ★ same residue
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

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-val431 (accessed [today's date]).

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