Is DRC7 p.Cys828Arg (c.2482T>C) pathogenic?

DRC7 p.Cys828Arg (c.2482T>C) is classified Uncertain significance in DRC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-18). AlphaMissense: likely pathogenic (0.9111); Very rare (popmax 0.000593%, nfe).

How common is DRC7 p.Cys828Arg (c.2482T>C) in the general population?

DRC7 p.Cys828Arg (c.2482T>C) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about DRC7 p.Cys828Arg (c.2482T>C)?

AlphaMissense predicts likely pathogenic (score 0.9111) — an in-silico prediction, not a clinical call.

DRC7 p.Cys828Arg

c.2482T>C · rs971319281 · VCV2272001

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9111 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9111	likely pathogenic · top 6% in DRC7
REVEL	0.419	indeterminate
SaProt	LLR -11.79	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 7.8	GERP 2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 33 kb · p 0.0015 · regional, not allelic
Overall
CADD	25.8	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 0.000593% European (non-Finnish) · 7/1,179,948 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000434% 7/1,613,546 alleles · very 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: DRC7
Protein: p.Cys828Arg
Coding: c.2482T>C
MANE Select: NM_001289162
dbSNP: rs971319281
Type: single nucleotide variant
Location: chr16:57731021 (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-cys828arg (accessed [today's date]).

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