Is DRC7 p.Arg794Cys (c.2380C>T) pathogenic?

DRC7 p.Arg794Cys (c.2380C>T) is classified Uncertain significance in DRC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-14). AlphaMissense: likely benign (0.1954); Ultra-rare (popmax 0.0256%, afr).

How common is DRC7 p.Arg794Cys (c.2380C>T) in the general population?

DRC7 p.Arg794Cys (c.2380C>T) is ultra-rare (popmax 0.0256%, afr) (gnomAD).

What do computational predictors say about DRC7 p.Arg794Cys (c.2380C>T)?

AlphaMissense predicts likely benign (score 0.1954) — an in-silico prediction, not a clinical call.

DRC7 p.Arg794Cys

c.2380C>T · VCV4014814

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1954 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0256%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1954	likely benign
REVEL	0.333	indeterminate
SaProt	LLR -9.23	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 4.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 33 kb · p 0.0015 · regional, not allelic
Overall
CADD	28.4	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 0.0256% African / African-American · 19/74,206 alleles

Filtering AF 0.0167% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0139%

Overall 0.00226% 36/1,594,936 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0256%	3,906
Middle Eastern	0.0171%	5,854
South Asian	0.00447%	22,361
East Asian	0.00227%	44,080
European (non-Finnish)	0.000941%	106,268

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: DRC7
Protein: p.Arg794Cys
Coding: c.2380C>T
MANE Select: NM_001289162
Type: single nucleotide variant
Location: chr16:57728573 (GRCh38)
Gene constraint: LOEUF 0.883 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.69 · 1 PDB

Full DRC7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DRC7 p.Ala510Pro Uncertain significance ★ ⚠ same type
DRC7 p.Ala605Val Uncertain significance ★ ⚠ same type
DRC7 p.Ala629Thr Uncertain significance ★ ⚠ same type
DRC7 p.Ala65Val Uncertain significance ★ ⚠ same type
DRC7 p.Ala709Val Uncertain significance ★ ⚠ same type
DRC7 p.Ala769Val Uncertain significance ★ ⚠ same type
DRC7 p.Arg103His Uncertain significance ★ ⚠ same type
DRC7 p.Arg112His 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/drc7-p-arg794cys (accessed [today's date]).

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