Is DRC5 p.Tyr130Cys (c.389A>G) pathogenic?

DRC5 p.Tyr130Cys (c.389A>G) is classified Uncertain significance in DRC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-15). AlphaMissense: likely pathogenic (0.684); Very rare (popmax 0.00446%, eas).

How common is DRC5 p.Tyr130Cys (c.389A>G) in the general population?

DRC5 p.Tyr130Cys (c.389A>G) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about DRC5 p.Tyr130Cys (c.389A>G)?

AlphaMissense predicts likely pathogenic (score 0.684) — an in-silico prediction, not a clinical call.

DRC5 p.Tyr130Cys

c.389A>G · rs574121622 · VCV2485143

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.684 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.684	likely pathogenic
REVEL	0.525	indeterminate
SaProt	LLR -15.88	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.7, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 7,641 bp · p 0.39 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00446% East Asian · 2/44,888 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000684% 10/1,461,858 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,444
Remaining individualsnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)	0.000593%	168,576

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.Tyr130Cys
Coding: c.389A>G
MANE Select: NM_182539
dbSNP: rs574121622
Type: single nucleotide variant
Location: chr6:44286421 (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.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-tyr130cys (accessed [today's date]).

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