Is DCAF17 p.His185Arg (c.554A>G) pathogenic?

DCAF17 p.His185Arg (c.554A>G) is classified Uncertain significance in DCAF17 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-24). AlphaMissense: likely benign (0.0719); Ultra-rare (popmax 0.0202%, amr); Associated with Woodhouse-Sakati syndrome.

What condition is associated with DCAF17 p.His185Arg (c.554A>G)?

DCAF17 p.His185Arg (c.554A>G) is associated with Woodhouse-Sakati syndrome (ClinVar).

How common is DCAF17 p.His185Arg (c.554A>G) in the general population?

DCAF17 p.His185Arg (c.554A>G) is ultra-rare (popmax 0.0202%, amr) (gnomAD).

How is Woodhouse-Sakati syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DCAF17 p.His185Arg (c.554A>G)?

AlphaMissense predicts likely benign (score 0.0719) — an in-silico prediction, not a clinical call.

DCAF17 p.His185Arg

c.554A>G · rs775985887 · VCV1405389

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0719 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0202%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Woodhouse-Sakati syndrome

Computational evidence

Protein change
AlphaMissense	0.0719	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -5.11	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 5.9	GERP 0.87, phastCons 0.97
Regional constraint	o/e 0.98	unconstrained · MANE · 34 kb · p 0.67 · regional, not allelic
Overall
CADD	17.9	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 0.0202% Admixed American · 12/59,374 alleles

Filtering AF 0.0116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00907%

Overall 0.00087% 14/1,608,838 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0202%	4,948
South Asian	0.00223%	44,888

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.His185Arg
Coding: c.554A>G
MANE Select: NM_025000
dbSNP: rs775985887
Type: single nucleotide variant
Location: chr2:171453140 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.38
Residue 185: a UniProt-annotated variant site (in)

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

Disease context

Woodhouse-Sakati syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Woodhouse-Sakati syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Childhood

Similar variants

DCAF17 p.His185Gln Benign/Likely benign ★★ same residue
DCAF17 p.His185fs Pathogenic ★ 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

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-his185arg (accessed [today's date]).

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