Is DCAF4 p.Arg366His (c.1097G>A) pathogenic?

DCAF4 p.Arg366His (c.1097G>A) is classified Uncertain significance in DCAF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely benign (0.0722); Very rare (popmax 0.00446%, eas).

How common is DCAF4 p.Arg366His (c.1097G>A) in the general population?

DCAF4 p.Arg366His (c.1097G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about DCAF4 p.Arg366His (c.1097G>A)?

AlphaMissense predicts likely benign (score 0.0722) — an in-silico prediction, not a clinical call.

DCAF4 p.Arg366His

c.1097G>A · rs141315052 · VCV2489964

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0722 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0722	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -7.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.3	GERP -2.7, phastCons 0.001
Regional constraint	o/e 0.89	unconstrained · MANE · 21 kb · p 0.0042 · regional, not allelic
Overall
CADD	14.64	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 0.00446% East Asian · 2/44,890 alleles

Filtering AF 0.00318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00286%

Overall 0.00347% 56/1,614,022 alleles · very rare exomes 54/1,461,852 · genomes 2/152,170 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,445
European (non-Finnish)	0.00415%	24,082
Remaining individualsnot grpmax-eligible	0.0032%	31,243
South Asian	0.0022%	45,547
Admixed American	0.00167%	59,998

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: DCAF4
Protein: p.Arg366His
Coding: c.1097G>A
MANE Select: NM_015604
dbSNP: rs141315052
Type: single nucleotide variant
Location: chr14:72955614 (GRCh38)
Gene constraint: LOEUF 0.787 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.34 · 1 PDB

Full DCAF4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCAF4 p.Ser28= Benign ★★ same type
DCAF4 p.Ser325Gly Likely benign ★★ same type
DCAF4 p.Ala125Val Uncertain significance ★ ⚠ same type
DCAF4 p.Ala168Gly Uncertain significance ★ ⚠ same type
DCAF4 p.Ala179Thr Uncertain significance ★ ⚠ same type
DCAF4 p.Ala233Val Uncertain significance ★ ⚠ same type
DCAF4 p.Ala285Ser Uncertain significance ★ ⚠ same type
DCAF4 p.Ala461Thr 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/dcaf4-p-arg366his (accessed [today's date]).

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