Is DRC8 p.Asp6Asn (c.16G>A) pathogenic?

DRC8 p.Asp6Asn (c.16G>A) is classified Uncertain significance in DRC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-09). Ultra-rare (popmax 0.0349%, mid).

How common is DRC8 p.Asp6Asn (c.16G>A) in the general population?

DRC8 p.Asp6Asn (c.16G>A) is ultra-rare (popmax 0.0349%, mid) (gnomAD).

DRC8 p.Asp6Asn

c.16G>A · rs201927564 · VCV2355217

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0349%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.143	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP 1.1, phastCons 0.99
Regional constraint	o/e 1.03	unconstrained · MANE · 117 kb · p 0.7 · regional, not allelic
Overall
CADD	15.64	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0349% Middle Eastern · 2/5,732 alleles

Filtering AF 0.00813% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00756%

Overall 0.0169% 259/1,535,132 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.373%	268
Remaining individualsnot grpmax-eligible	0.0534%	1,872
Middle Easterngrpmax	0.0349%	2,866
European (non-Finnish)	0.00958%	10,436
Admixed American	0.00588%	17,003
South Asian	0.00476%	21,027
African / African-American	0.00277%	36,047

Ashkenazi Jewish 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: DRC8
Protein: p.Asp6Asn
Coding: c.16G>A
MANE Select: NM_032328
dbSNP: rs201927564
Type: single nucleotide variant
Location: chr1:244970434 (GRCh38)
Structure: AlphaFold pLDDT 65.45 · 1 PDB
Residue 6: the 'disordered' region

Full DRC8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DRC8 p.Asp6Tyr Uncertain significance ★ ⚠ same residue
DRC8 p.Phe73= Benign ★★ same type
DRC8 p.Ala13Thr Uncertain significance ★ ⚠ same type
DRC8 p.Asp152Val Uncertain significance ★ same type
DRC8 p.Ile141Thr Uncertain significance ★ same type
DRC8 p.Val36Leu Uncertain significance ★ ⚠ same type
EFCAB2 p.Glu116Lys Uncertain significance ★ ⚠ same type
EFCAB2 p.Glu4Lys 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/drc8-p-asp6asn (accessed [today's date]).

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