Is DRC5 p.Lys39Arg (c.116A>G) pathogenic?

DRC5 p.Lys39Arg (c.116A>G) is classified Uncertain significance in DRC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-12). AlphaMissense: likely benign (0.0694); Ultra-rare (popmax 0.0178%, eas).

How common is DRC5 p.Lys39Arg (c.116A>G) in the general population?

DRC5 p.Lys39Arg (c.116A>G) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about DRC5 p.Lys39Arg (c.116A>G)?

AlphaMissense predicts likely benign (score 0.0694) — an in-silico prediction, not a clinical call.

DRC5 p.Lys39Arg

c.116A>G · rs778750412 · VCV3175368

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0694 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0694	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -5.51	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 0.18	GERP -0.058, phastCons 0.3
Regional constraint	o/e 0.97	unconstrained · MANE · 7,641 bp · p 0.39 · regional, not allelic
Overall
CADD	3.057	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 0.0178% East Asian · 8/44,892 alleles

Filtering AF 0.00883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.000496% 8/1,614,044 alleles · ultra-rare

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: DRC5
Protein: p.Lys39Arg
Coding: c.116A>G
MANE Select: NM_182539
dbSNP: rs778750412
Type: single nucleotide variant
Location: chr6:44287710 (GRCh38)
Structure: AlphaFold pLDDT 83.02 · 1 PDB
Residue 39: the 'disordered' region

Full DRC5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DRC5 p.Ala351Asp Uncertain significance ★ ⚠ same type
DRC5 p.Ala381Thr Uncertain significance ★ ⚠ same type
DRC5 p.Ala385Gly Uncertain significance ★ ⚠ same type
DRC5 p.Arg133His Uncertain significance ★ ⚠ same type
DRC5 p.Arg133Pro Uncertain significance ★ ⚠ same type
DRC5 p.Arg158Gln Uncertain significance ★ ⚠ same type
DRC5 p.Arg185Gly Uncertain significance ★ ⚠ same type
DRC5 p.Arg185Trp 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/drc5-p-lys39arg (accessed [today's date]).

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