Is DCAF6 p.Arg471Cys (c.1411C>T) pathogenic?

DCAF6 p.Arg471Cys (c.1411C>T) is classified Uncertain significance in DCAF6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-08). Very rare (popmax 0.00309%, nfe).

How common is DCAF6 p.Arg471Cys (c.1411C>T) in the general population?

DCAF6 p.Arg471Cys (c.1411C>T) is very rare (popmax 0.00309%, nfe) (gnomAD).

DCAF6 p.Arg471Cys

c.1411C>T · VCV3270990

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00309%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.308	indeterminate
Splicing
SpliceAI	Δ0.41	acceptor loss, 32 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 7.6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 63 kb · p 0.0024 · regional, not allelic
Overall
CADD	28.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00309% European (non-Finnish) · 35/1,133,920 alleles

Filtering AF 0.00224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00198%

Overall 0.00544% 83/1,526,630 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0703%	1,422
Remaining individualsnot grpmax-eligible	0.00848%	11,796
European (non-Finnish)grpmax	0.00309%	32,398
African / African-American	0.00278%	36,024

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: DCAF6
Protein: p.Arg471Cys
Coding: c.1411C>T
MANE Select: NM_001198956
Type: single nucleotide variant
Location: chr1:168015813 (GRCh38)
Gene constraint: LOEUF 0.567 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 64.23 · 1 PDB
Residue 471: the 'disordered' region

Full DCAF6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCAF6 p.Arg471His Uncertain significance ★ same residue
DCAF6 p.Thr644Ile Benign ★★ same type
ADCY10 c.292+6G>A Uncertain significance ★ same type
ADCY10 p.Gln283His Uncertain significance ★ ⚠ same type
ADCY10 p.Glu7Val Uncertain significance ★ ⚠ same type
ADCY10 p.Met237Thr Uncertain significance ★ ⚠ same type
ADCY10 p.Thr235Ser Uncertain significance ★ ⚠ same type
ADCY10 p.Thr254Met Conflicting classifications of pathogenicity ★ ⚠ 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/dcaf6-p-arg471cys (accessed [today's date]).

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