Is DCAF6 p.Arg366Gln (c.1097G>A) pathogenic?

DCAF6 p.Arg366Gln (c.1097G>A) is classified Uncertain significance in DCAF6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-14). AlphaMissense: likely benign (0.1003); Rare (popmax 0.137%, mid).

How common is DCAF6 p.Arg366Gln (c.1097G>A) in the general population?

DCAF6 p.Arg366Gln (c.1097G>A) is rare (popmax 0.137%, mid) (gnomAD).

What do computational predictors say about DCAF6 p.Arg366Gln (c.1097G>A)?

AlphaMissense predicts likely benign (score 0.1003) — an in-silico prediction, not a clinical call.

DCAF6 p.Arg366Gln

c.1097G>A · rs370291307 · VCV2271424

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1003 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.137%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1003	likely benign
REVEL	0.424	indeterminate
SaProt	LLR -8.12	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.5, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 63 kb · p 0.0024 · regional, not allelic
Overall
CADD	26.7	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 0.137% Middle Eastern · 8/5,858 alleles

Filtering AF 0.0679% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0495%

Overall 0.00782% 126/1,612,210 alleles · rare exomes 111/1,460,072 · genomes 15/152,138 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.137%	732
African / African-American	0.0374%	2,673
Remaining individualsnot grpmax-eligible	0.0256%	3,899
Admixed American	0.0134%	7,483
European (non-Finnish)	0.00534%	18,715
South Asian	0.0033%	30,314

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.Arg366Gln
Coding: c.1097G>A
MANE Select: NM_001198956
dbSNP: rs370291307
Type: single nucleotide variant
Location: chr1:168003969 (GRCh38)
Gene constraint: LOEUF 0.567 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 64.23 · 1 PDB
Residue 366: the 'disordered' region

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

Similar variants

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
DCAF6 p.Ala295Val 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/dcaf6-p-arg366gln (accessed [today's date]).

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