Is DCT p.Arg233Ter (c.697C>T) pathogenic?

DCT p.Arg233Ter (c.697C>T) is classified Pathogenic/Likely pathogenic in DCT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-05). Ultra-rare (popmax 0.0134%, sas); Associated with oculocutaneous albinism type 8.

What condition is associated with DCT p.Arg233Ter (c.697C>T)?

DCT p.Arg233Ter (c.697C>T) is associated with oculocutaneous albinism type 8 (ClinVar).

How common is DCT p.Arg233Ter (c.697C>T) in the general population?

DCT p.Arg233Ter (c.697C>T) is ultra-rare (popmax 0.0134%, sas) (gnomAD).

How is Oculocutaneous albinism type 8 inherited?

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

DCT p.Arg233Ter

c.697C>T · VCV3779220

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, sas)

Conditions

oculocutaneous albinism type 8

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 8
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.7	GERP 0.15, phastCons 0.97
Overall
CADD	37.0	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 0.0134% South Asian · 12/89,852 alleles

Filtering AF 0.0077% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.006%

Overall 0.00131% 21/1,604,686 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0134%	7,488
East Asian	0.0045%	22,206
African / African-American	0.00269%	37,133
European (non-Finnish)	0.000426%	234,992

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.Arg233Ter
Coding: c.697C>T
MANE Select: NM_001922
Type: single nucleotide variant
Location: chr13:94465799 (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.Arg233Leu Uncertain significance ★ ⚠ same residue
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-arg233ter (accessed [today's date]).

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