Is DRC5 p.Arg62Leu (c.185G>T) pathogenic?

DRC5 p.Arg62Leu (c.185G>T) is classified Uncertain significance in DRC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-13). AlphaMissense: likely pathogenic (0.6105); Rare (popmax 0.11%, amr).

How common is DRC5 p.Arg62Leu (c.185G>T) in the general population?

DRC5 p.Arg62Leu (c.185G>T) is rare (popmax 0.11%, amr) (gnomAD).

What do computational predictors say about DRC5 p.Arg62Leu (c.185G>T)?

AlphaMissense predicts likely pathogenic (score 0.6105) — an in-silico prediction, not a clinical call.

DRC5 p.Arg62Leu

c.185G>T · rs201144307 · VCV2243216

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6105 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.11%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6105	likely pathogenic
REVEL	0.352	indeterminate
SaProt	LLR -9.83	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 7,641 bp · p 0.39 · regional, not allelic
Overall
CADD	24.4	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 0.11% Admixed American · 66/59,992 alleles

Filtering AF 0.0887% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0809%

Overall 0.00415% 67/1,613,966 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.11%	909
European (non-Finnish)	8.47e-05%	1,180,034

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.Arg62Leu
Coding: c.185G>T
MANE Select: NM_182539
dbSNP: rs201144307
Type: single nucleotide variant
Location: chr6:44287641 (GRCh38)
Structure: AlphaFold pLDDT 83.02 · 1 PDB

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

Similar variants

DRC5 p.Arg62Cys Uncertain significance ★ ⚠ same residue
TCTE1 p.Arg62His Uncertain significance ★ ⚠ same residue
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

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-arg62leu (accessed [today's date]).

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