Is DRC3 p.Thr449Arg (c.1346C>G) pathogenic?

DRC3 p.Thr449Arg (c.1346C>G) is classified Uncertain significance in DRC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: likely benign (0.1662); Absent from gnomAD v4.1.

How common is DRC3 p.Thr449Arg (c.1346C>G) in the general population?

DRC3 p.Thr449Arg (c.1346C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DRC3 p.Thr449Arg (c.1346C>G)?

AlphaMissense predicts likely benign (score 0.1662) — an in-silico prediction, not a clinical call.

DRC3 p.Thr449Arg

c.1346C>G · VCV4662110

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1662 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1662	likely benign
REVEL	0.389	indeterminate
SaProt	LLR -9.19	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.9	GERP 1.8, phastCons 1
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

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: DRC3
Protein: p.Thr449Arg
Coding: c.1346C>G
MANE Select: NM_145691 · reported on NM_031294
Type: single nucleotide variant
Location: chr17:18016083 (GRCh38)

Full DRC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/drc3-p-thr449arg (accessed [today's date]).

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