Is DCT p.Val186fs (c.555dup) pathogenic?

DCT p.Val186fs (c.555dup) is classified Likely pathogenic in DCT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-02). Ultra-rare (popmax 0.0232%, nfe); Associated with oculocutaneous albinism type 8.

What condition is associated with DCT p.Val186fs (c.555dup)?

DCT p.Val186fs (c.555dup) is associated with oculocutaneous albinism type 8 (ClinVar).

How common is DCT p.Val186fs (c.555dup) in the general population?

DCT p.Val186fs (c.555dup) is ultra-rare (popmax 0.0232%, nfe) (gnomAD).

How is Oculocutaneous albinism type 8 inherited?

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

DCT p.Val186fs

c.555dup · VCV3893090

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0232%, nfe)

Conditions

oculocutaneous albinism type 8

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0232% European (non-Finnish) · 274/1,180,040 alleles

Filtering AF 0.0209% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0201%

Overall 0.0177% 285/1,614,026 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0232%	4,307
African / African-American	0.00668%	14,980
Remaining individualsnot grpmax-eligible	0.0064%	15,621
South Asian	0.0022%	45,546

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: DCT
Protein: p.Val186fs
Coding: c.555dup
MANE Select: NM_001922
Type: Duplication
Location: chr13:94468785 (GRCh38)
Gene constraint: LOEUF 1.101 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.33 · 1 PDB

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

Disease context

oculocutaneous albinism type 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Oculocutaneous albinism type 8 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

DCT p.Arg233Ter Pathogenic/Likely pathogenic ★★ same condition
DCT p.Arg326Ter Pathogenic ★ same condition
DCT p.Trp71Ter Pathogenic ★ same condition
DCT p.Gly213Glu Uncertain significance ★ ⚠ same condition
DCT p.Ser34Arg Uncertain significance ★ ⚠ same condition
DCT p.Val285Leu Likely benign ★ ⚠ same condition
DCT p.Cys40Ser Pathogenic/Likely pathogenic same condition
DCT p.Cys61Trp Pathogenic/Likely pathogenic 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/dct-p-val186fs (accessed [today's date]).

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