Is DCT p.Ser34Arg (c.100A>C) pathogenic?

DCT p.Ser34Arg (c.100A>C) is classified Uncertain significance in DCT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-22). AlphaMissense: likely benign (0.2535); Rare (popmax 0.372%, sas); Associated with oculocutaneous albinism type 8.

What condition is associated with DCT p.Ser34Arg (c.100A>C)?

DCT p.Ser34Arg (c.100A>C) is associated with oculocutaneous albinism type 8 (ClinVar).

How common is DCT p.Ser34Arg (c.100A>C) in the general population?

DCT p.Ser34Arg (c.100A>C) is rare (popmax 0.372%, sas) (gnomAD).

How is Oculocutaneous albinism type 8 inherited?

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

What do computational predictors say about DCT p.Ser34Arg (c.100A>C)?

AlphaMissense predicts likely benign (score 0.2535) — an in-silico prediction, not a clinical call.

DCT p.Ser34Arg

c.100A>C · rs567859263 · VCV2688920

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2535 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.372%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

oculocutaneous albinism type 8

Computational evidence

Protein change
AlphaMissense	0.2535	likely benign
REVEL	0.356	indeterminate
SaProt	LLR -8.07	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.049	GERP -0.85
Regional constraint	o/e 1.05	unconstrained · MANE · 39 kb · p 0.21 · regional, not allelic
Overall
CADD	18.95	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.372% South Asian · 339/91,084 alleles

Filtering AF 0.34% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.327%

Overall 0.0224% 361/1,614,082 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.372%	269
Remaining individualsnot grpmax-eligible	0.0288%	3,472
Admixed American	0.00167%	60,032
European (non-Finnish)	0.000254%	393,298

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.Ser34Arg
Coding: c.100A>C
MANE Select: NM_001922
dbSNP: rs567859263
Type: single nucleotide variant
Location: chr13:94479156 (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

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DCT p.Gly213Glu Uncertain significance ★ ⚠ same condition
DCT p.Val285Leu Likely benign ★ ⚠ same condition
DCT p.Cys40Ser Pathogenic/Likely pathogenic same condition
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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-ser34arg (accessed [today's date]).

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