Is DCT p.Cys40Ser (c.118T>A) pathogenic?

DCT p.Cys40Ser (c.118T>A) is classified Pathogenic/Likely pathogenic in DCT (ClinVar, No assertion criteria, 2 submitters; last evaluated 2021-04-20). AlphaMissense: likely pathogenic (0.9796); Very rare (popmax 0.00415%, nfe); Associated with albinism.

What condition is associated with DCT p.Cys40Ser (c.118T>A)?

DCT p.Cys40Ser (c.118T>A) is associated with albinism, oculocutaneous albinism type 8 (ClinVar).

How common is DCT p.Cys40Ser (c.118T>A) in the general population?

DCT p.Cys40Ser (c.118T>A) is very rare (popmax 0.00415%, nfe) (gnomAD).

What do computational predictors say about DCT p.Cys40Ser (c.118T>A)?

AlphaMissense predicts likely pathogenic (score 0.9796) — an in-silico prediction, not a clinical call.

DCT p.Cys40Ser

c.118T>A · rs370729240 · VCV929863

Pathogenic/Likely pathogenic No assertion criteria

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9796 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00415%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

albinism

Computational evidence

Protein change
AlphaMissense	0.9796	likely pathogenic ✓ concordant with ClinVar · top 2% in DCT
REVEL	0.972	strongly pathogenic-leaning
SaProt	LLR -8.75	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 39 kb · p 0.21 · regional, not allelic
Overall
CADD	25.7	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

Grpmax group 0.00415% European (non-Finnish) · 49/1,179,968 alleles

Filtering AF 0.00318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00286%

Overall 0.0031% 50/1,613,728 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00415%	24,081
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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.Cys40Ser
Coding: c.118T>A
MANE Select: NM_001922
dbSNP: rs370729240
Type: single nucleotide variant
Location: chr13:94479138 (GRCh38)
Gene constraint: LOEUF 1.101 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.33 · 1 PDB
Residue 40: a UniProt-annotated variant site (in oca8)

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

Disease context

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

Also linked: oculocutaneous albinism type 8

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.Cys61Trp Pathogenic/Likely pathogenic same condition
DCT p.Gly59Val 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-cys40ser (accessed [today's date]).

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