Is DCTD p.Asn54Ser (c.161A>G) pathogenic?

DCTD p.Asn54Ser (c.161A>G) is classified Uncertain significance in DCTD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). AlphaMissense: likely pathogenic (0.8213); Very rare (popmax 8.47e-05%, nfe).

How common is DCTD p.Asn54Ser (c.161A>G) in the general population?

DCTD p.Asn54Ser (c.161A>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about DCTD p.Asn54Ser (c.161A>G)?

AlphaMissense predicts likely pathogenic (score 0.8213) — an in-silico prediction, not a clinical call.

DCTD p.Asn54Ser

c.161A>G · VCV4238263

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8213 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8213	likely pathogenic
REVEL	0.67	pathogenic-leaning
SaProt	LLR -14.22	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 7.8	GERP 2.6, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 24 kb · p 0.69 · regional, not allelic
Overall
CADD	24.6	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 8.47e-05% European (non-Finnish) · 1/1,180,034 alleles

Overall 6.84e-05% 1/1,461,884 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.Asn54Ser
Coding: c.161A>G
MANE Select: NM_001921
Type: single nucleotide variant
Location: chr4:182915006 (GRCh38)
Gene constraint: LOEUF 1.924 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.43 · 1 PDB
Residue 54: the cmp/dcmp-type deaminase domain; a β-strand

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.Asp76Val Uncertain significance ★ ⚠ same type
DCTD p.Asp97Glu Uncertain significance ★ ⚠ same type
DCTD p.Cys40Tyr Uncertain significance ★ ⚠ same type
DCTD p.Glu137Lys 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-asn54ser (accessed [today's date]).

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