Is DCT p.Glu119Lys (c.355G>A) pathogenic?

DCT p.Glu119Lys (c.355G>A) is classified Uncertain significance in DCT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-16). AlphaMissense: likely benign (0.1064); Ultra-rare (popmax 0.0154%, sas); Associated with Inborn genetic diseases.

What condition is associated with DCT p.Glu119Lys (c.355G>A)?

DCT p.Glu119Lys (c.355G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DCT p.Glu119Lys (c.355G>A) in the general population?

DCT p.Glu119Lys (c.355G>A) is ultra-rare (popmax 0.0154%, sas) (gnomAD).

What do computational predictors say about DCT p.Glu119Lys (c.355G>A)?

AlphaMissense predicts likely benign (score 0.1064) — an in-silico prediction, not a clinical call.

DCT p.Glu119Lys

c.355G>A · rs1367925937 · VCV2279014

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1064 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0154%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1064	likely benign
REVEL	0.145	moderately benign-leaning
SaProt	LLR -11.56	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.016	GERP -3.6
Regional constraint	o/e 1.05	unconstrained · MANE · 39 kb · p 0.21 · regional, not allelic
Overall
CADD	16.89	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 0.0154% South Asian · 14/91,076 alleles

Filtering AF 0.0092% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00735%

Overall 0.00105% 17/1,613,988 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0154%	6,505
Remaining individualsnot grpmax-eligible	0.0032%	31,240
European (non-Finnish)	8.47e-05%	1,179,999

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.Glu119Lys
Coding: c.355G>A
MANE Select: NM_001922
dbSNP: rs1367925937
Type: single nucleotide variant
Location: chr13:94468986 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DCT c.1180-2098C>T Uncertain significance ★ same condition
DCT c.1180-2111A>G Uncertain significance ★ same condition
DCT p.Ala144Thr Uncertain significance ★ ⚠ same condition
DCT p.Ala206Thr Uncertain significance ★ ⚠ same condition
DCT p.Ala357Glu Uncertain significance ★ ⚠ same condition
DCT p.Ala381Thr Uncertain significance ★ ⚠ same condition
DCT p.Ala386Thr Uncertain significance ★ ⚠ same condition
DCT p.Arg202Cys 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/dct-p-glu119lys (accessed [today's date]).

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