Is DRC11 p.Arg683His (c.2048G>A) pathogenic?

DRC11 p.Arg683His (c.2048G>A) is classified Uncertain significance in DRC11 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-18). AlphaMissense: likely benign (0.1007); Ultra-rare (popmax 0.0156%, eas).

How common is DRC11 p.Arg683His (c.2048G>A) in the general population?

DRC11 p.Arg683His (c.2048G>A) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about DRC11 p.Arg683His (c.2048G>A)?

AlphaMissense predicts likely benign (score 0.1007) — an in-silico prediction, not a clinical call.

DRC11 p.Arg683His

c.2048G>A · rs367642284 · VCV3110387

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1007 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1007	likely benign
REVEL	0.616	indeterminate
SaProt	LLR -9.19	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 183 kb · p 0.19 · regional, not allelic
Overall
CADD	25.4	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 0.0156% East Asian · 7/44,892 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00514%

Overall 0.00254% 41/1,613,800 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,413
Admixed American	0.00667%	15,002
African / African-American	0.00401%	24,957
Remaining individualsnot grpmax-eligible	0.0032%	31,232
South Asian	0.0022%	45,546
European (non-Finnish)	0.00195%	51,299

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: DRC11
Protein: p.Arg683His
Coding: c.2048G>A
MANE Select: NM_024726
dbSNP: rs367642284
Type: single nucleotide variant
Location: chr2:236338291 (GRCh38)
Structure: AlphaFold pLDDT 79.87 · 1 PDB

Full DRC11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DRC11 p.Ala143Val Uncertain significance ★ ⚠ same type
DRC11 p.Ala574Pro Uncertain significance ★ ⚠ same type
DRC11 p.Ala594Val Uncertain significance ★ ⚠ same type
DRC11 p.Ala735Val Uncertain significance ★ ⚠ same type
DRC11 p.Ala804Gly Uncertain significance ★ ⚠ same type
DRC11 p.Ala806Val Uncertain significance ★ ⚠ same type
DRC11 p.Arg224His Uncertain significance ★ ⚠ same type
DRC11 p.Arg531Cys 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/drc11-p-arg683his (accessed [today's date]).

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