Is DCAF17 p.Arg178Gln (c.533G>A) pathogenic?

DCAF17 p.Arg178Gln (c.533G>A) is classified Conflicting classifications of pathogenicity in DCAF17 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-25). AlphaMissense: likely benign (0.0769); Ultra-rare (popmax 0.01%, amr); Associated with Inborn genetic diseases.

What condition is associated with DCAF17 p.Arg178Gln (c.533G>A)?

DCAF17 p.Arg178Gln (c.533G>A) is associated with Inborn genetic diseases, Woodhouse-Sakati syndrome (ClinVar).

How common is DCAF17 p.Arg178Gln (c.533G>A) in the general population?

DCAF17 p.Arg178Gln (c.533G>A) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about DCAF17 p.Arg178Gln (c.533G>A)?

AlphaMissense predicts likely benign (score 0.0769) — an in-silico prediction, not a clinical call.

DCAF17 p.Arg178Gln

c.533G>A · rs202231211 · VCV332265

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0769 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0769	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -6.57	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 0.83, phastCons 0.97
Regional constraint	o/e 0.98	unconstrained · MANE · 34 kb · p 0.67 · regional, not allelic
Overall
CADD	19.61	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/59,972 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.0165% 266/1,612,228 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.595%	168
Remaining individualsnot grpmax-eligible	0.0593%	1,687
Admixed Americangrpmax	0.01%	9,995
European (non-Finnish)	0.00373%	26,787
African / African-American	0.00267%	37,422
East Asian	0.00223%	44,856

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: DCAF17
Protein: p.Arg178Gln
Coding: c.533G>A
MANE Select: NM_025000
dbSNP: rs202231211
Type: single nucleotide variant
Location: chr2:171449953 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.38

Full DCAF17 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Woodhouse-Sakati syndrome

Similar variants

DCAF17 p.Arg178Trp Uncertain significance ★★ ⚠ same residue
DCAF17 c.127-1G>C Pathogenic/Likely pathogenic ★★ same condition
DCAF17 p.Arg194Ter Pathogenic/Likely pathogenic ★★ same condition
DCAF17 p.Met1Val Pathogenic/Likely pathogenic ★★ same condition
DCAF17 p.Trp129Ter Pathogenic ★★ same condition
DCAF17 p.Trp302Ter Pathogenic ★★ same condition
DCAF17 c.1266+4T>C Uncertain significance ★★ same condition
DCAF17 c.*126A>T Uncertain significance ★★ same condition

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/dcaf17-p-arg178gln (accessed [today's date]).

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