Is DCTD p.Lys115Thr (c.344A>C) pathogenic?

DCTD p.Lys115Thr (c.344A>C) is classified Uncertain significance in DCTD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-25). AlphaMissense: likely pathogenic (0.9688); Very rare (popmax 0.00127%, nfe).

How common is DCTD p.Lys115Thr (c.344A>C) in the general population?

DCTD p.Lys115Thr (c.344A>C) is very rare (popmax 0.00127%, nfe) (gnomAD).

What do computational predictors say about DCTD p.Lys115Thr (c.344A>C)?

AlphaMissense predicts likely pathogenic (score 0.9688) — an in-silico prediction, not a clinical call.

DCTD p.Lys115Thr

c.344A>C · VCV3500175

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9688 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00127%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9688	likely pathogenic
REVEL	0.733	pathogenic-leaning
SaProt	LLR -15.41	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 24 kb · p 0.69 · regional, not allelic
Overall
CADD	29.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00127% European (non-Finnish) · 15/1,177,854 alleles

Filtering AF 0.000765% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000606%

Overall 0.00103% 15/1,459,462 alleles · very rare

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: DCTD
Protein: p.Lys115Thr
Coding: c.344A>C
MANE Select: NM_001921
Type: single nucleotide variant
Location: chr4:182894506 (GRCh38)
Gene constraint: LOEUF 1.924 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.43 · 1 PDB
Residue 115: the cmp/dcmp-type deaminase domain; an α-helix

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

Similar variants

DCTD p.Ala85= Benign ★★ same type
DCTD p.Ala23Gly Uncertain significance ★ ⚠ same type
DCTD p.Ala39Thr Uncertain significance ★ ⚠ same type
DCTD p.Arg153Trp Uncertain significance ★ ⚠ same type
DCTD p.Asn54Ser Uncertain significance ★ ⚠ same type
DCTD p.Asp76Val Uncertain significance ★ ⚠ same type
DCTD p.Asp97Glu Uncertain significance ★ ⚠ same type
DCTD p.Cys40Tyr Uncertain significance ★ ⚠ same type

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/dctd-p-lys115thr (accessed [today's date]).

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