Is DRC4 p.Arg347Gln (c.1040G>A) pathogenic?

DRC4 p.Arg347Gln (c.1040G>A) is classified Likely benign in DRC4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-07-11). AlphaMissense: likely benign (0.0596); Very rare (popmax 0.00345%, amr); Associated with Inborn genetic diseases.

What condition is associated with DRC4 p.Arg347Gln (c.1040G>A)?

DRC4 p.Arg347Gln (c.1040G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DRC4 p.Arg347Gln (c.1040G>A) in the general population?

DRC4 p.Arg347Gln (c.1040G>A) is very rare (popmax 0.00345%, amr) (gnomAD).

What do computational predictors say about DRC4 p.Arg347Gln (c.1040G>A)?

AlphaMissense predicts likely benign (score 0.0596) — an in-silico prediction, not a clinical call.

DRC4 p.Arg347Gln

c.1040G>A · rs774683666 · VCV2260299

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0596 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00345%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0596	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -5.86	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 -0.24
Regional constraint	o/e 1.12	unconstrained · MANE · 21 kb · p 0.0024 · regional, not allelic
Overall
CADD	1.842	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 0.00345% Admixed American · 2/57,938 alleles

Filtering AF 0.000573% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000368%

Overall 0.00104% 15/1,445,724 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00345%	28,969
East Asian	0.00228%	43,928
South Asian	0.00113%	88,324
European (non-Finnish)	0.000938%	106,595

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: DRC4
Protein: p.Arg347Gln
Coding: c.1040G>A
MANE Select: NM_001481
dbSNP: rs774683666
Type: single nucleotide variant
Location: chr16:90040328 (GRCh38)
Structure: AlphaFold pLDDT 85.12 · 1 PDB
Residue 347: a UniProt-annotated variant site (in cild33; loss of localization to cilia; abnormal cilia with axonemal disorganization)

Full DRC4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DRC4 p.Arg347Trp Uncertain significance ★★ ⚠ same residue
DRC4 p.Ala280Thr Uncertain significance ★★ ⚠ same condition
DRC4 p.Ala460Pro Uncertain significance ★★ ⚠ same condition
DRC4 p.Arg203Gln Uncertain significance ★★ ⚠ same condition
DRC4 p.Arg278Cys Uncertain significance ★★ ⚠ same condition
DRC4 p.Arg342Trp Uncertain significance ★★ ⚠ same condition
DRC4 p.Arg369Cys Uncertain significance ★★ ⚠ same condition
DRC4 p.Asp239Tyr Uncertain significance ★★ ⚠ same condition

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/drc4-p-arg347gln (accessed [today's date]).

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