Is DRC7 p.Arg583Trp (c.1747C>T) pathogenic?

DRC7 p.Arg583Trp (c.1747C>T) is classified Likely benign in DRC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-01). AlphaMissense: ambiguous (0.4631); Rare (popmax 0.684%, nfe).

How common is DRC7 p.Arg583Trp (c.1747C>T) in the general population?

DRC7 p.Arg583Trp (c.1747C>T) is rare (popmax 0.684%, nfe) (gnomAD).

What do computational predictors say about DRC7 p.Arg583Trp (c.1747C>T)?

AlphaMissense predicts ambiguous (score 0.4631) — an in-silico prediction, not a clinical call.

DRC7 p.Arg583Trp

c.1747C>T · rs114195136 · VCV2646562

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4631 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.684%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4631	ambiguous
REVEL	0.255	benign-leaning
SaProt	LLR -13.02	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP -2.2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 33 kb · p 0.0015 · regional, not allelic
Overall
CADD	25.2	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 0.684% European (non-Finnish) · 8,073/1,179,704 alleles

Filtering AF 0.672% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.667%

Overall 0.572% 9,226/1,612,960 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.06%	94
European (non-Finnish)grpmax	0.684%	146
Remaining individualsnot grpmax-eligible	0.471%	212
Amishnot grpmax-eligible	0.439%	228
Admixed American	0.137%	731
African / African-American	0.107%	937
Ashkenazi Jewishnot grpmax-eligible	0.0642%	1,557
South Asian	0.0022%	45,488

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg583Trp
Coding: c.1747C>T
MANE Select: NM_001289162
dbSNP: rs114195136
Type: single nucleotide variant
Location: chr16:57724824 (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.Arg583Gln Uncertain significance ★ ⚠ same residue
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

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-arg583trp (accessed [today's date]).

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