Is DCTD p.Asp97Glu (c.291T>A) pathogenic?

DCTD p.Asp97Glu (c.291T>A) is classified Uncertain significance in DCTD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-23). AlphaMissense: ambiguous (0.5477); Very rare (popmax 0.0011%, sas).

How common is DCTD p.Asp97Glu (c.291T>A) in the general population?

DCTD p.Asp97Glu (c.291T>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about DCTD p.Asp97Glu (c.291T>A)?

AlphaMissense predicts ambiguous (score 0.5477) — an in-silico prediction, not a clinical call.

DCTD p.Asp97Glu

c.291T>A · rs772271392 · VCV2246847

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5477 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5477	ambiguous
REVEL	0.221	benign-leaning
SaProt	LLR -10.58	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP -5.3	GERP -4.7
Regional constraint	o/e 0.97	unconstrained · MANE · 24 kb · p 0.69 · regional, not allelic
Overall
CADD	0.45	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 0.0011% South Asian · 1/91,090 alleles

Overall 0.000657% 1/152,252 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.Asp97Glu
Coding: c.291T>A
MANE Select: NM_001921
dbSNP: rs772271392
Type: single nucleotide variant
Location: chr4:182894559 (GRCh38)
Gene constraint: LOEUF 1.924 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.43 · 1 PDB
Residue 97: the cmp/dcmp-type deaminase domain

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.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-asp97glu (accessed [today's date]).

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