Is DRC3 p.Glu224Asp (c.672G>C) pathogenic?

DRC3 p.Glu224Asp (c.672G>C) is classified Uncertain significance in DRC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-01). AlphaMissense: likely benign (0.1111); Ultra-rare (popmax 0.0324%, nfe).

How common is DRC3 p.Glu224Asp (c.672G>C) in the general population?

DRC3 p.Glu224Asp (c.672G>C) is ultra-rare (popmax 0.0324%, nfe) (gnomAD).

What do computational predictors say about DRC3 p.Glu224Asp (c.672G>C)?

AlphaMissense predicts likely benign (score 0.1111) — an in-silico prediction, not a clinical call.

DRC3 p.Glu224Asp

c.672G>C · rs747487490 · VCV2363434

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1111 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0324%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1111	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -6.94	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.2	GERP -2.2, phastCons 0.75
Overall
CADD	5.067	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

Grpmax group 0.0324% European (non-Finnish) · 372/1,149,122 alleles

Filtering AF 0.0296% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0286%

Overall 0.0248% 386/1,554,758 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0324%	3,089
Remaining individualsnot grpmax-eligible	0.0149%	6,706
African / African-American	0.00684%	14,629

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: DRC3
Protein: p.Glu224Asp
Coding: c.672G>C
MANE Select: NM_133180 · reported on NM_031294
dbSNP: rs747487490
Type: single nucleotide variant
Location: chr17:17994379 (GRCh38)
Structure: AlphaFold pLDDT 75.86 · 2 PDB
Residue 224: the 'disordered' region

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

Similar variants

DRC3 p.Ala201Val Uncertain significance ★ ⚠ same type
DRC3 p.Ala221Thr Uncertain significance ★ ⚠ same type
DRC3 p.Ala228Val Uncertain significance ★ ⚠ same type
DRC3 p.Ala239Thr Uncertain significance ★ ⚠ same type
DRC3 p.Arg120Gln Uncertain significance ★ ⚠ same type
DRC3 p.Arg142Trp Uncertain significance ★ ⚠ same type
DRC3 p.Arg191Gln Uncertain significance ★ ⚠ same type
DRC3 p.Arg192Cys 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/drc3-p-glu224asp (accessed [today's date]).

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