Is DTD2 p.Gln121Pro (c.362A>C) pathogenic?

DTD2 p.Gln121Pro (c.362A>C) is classified Uncertain significance in DTD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: likely pathogenic (0.6608); Absent from gnomAD v4.1.

How common is DTD2 p.Gln121Pro (c.362A>C) in the general population?

DTD2 p.Gln121Pro (c.362A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DTD2 p.Gln121Pro (c.362A>C)?

AlphaMissense predicts likely pathogenic (score 0.6608) — an in-silico prediction, not a clinical call.

DTD2 p.Gln121Pro

c.362A>C · VCV4662304

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6608 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6608	likely pathogenic
REVEL	0.253	benign-leaning
SaProt	LLR -12.55	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 0.65, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 9,261 bp · p 0.029 · regional, not allelic
Overall
CADD	22.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DTD2
Protein: p.Gln121Pro
Coding: c.362A>C
MANE Select: NM_080664
Type: single nucleotide variant
Location: chr14:31448274 (GRCh38)
Gene constraint: LOEUF 1.429 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.31

Full DTD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DTD2 p.Ala12Glu Uncertain significance ★ ⚠ same type
DTD2 p.Arg102Gly Uncertain significance ★ ⚠ same type
DTD2 p.Gly149Arg Uncertain significance ★ ⚠ same type
DTD2 p.Ile166Thr Uncertain significance ★ ⚠ same type
DTD2 p.Leu13Phe Uncertain significance ★ ⚠ same type
DTD2 p.Met104Arg Uncertain significance ★ ⚠ same type
DTD2 p.Met60Thr Uncertain significance ★ ⚠ same type
DTD2 p.Phe168Ile 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/dtd2-p-gln121pro (accessed [today's date]).

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