Is DCAF17 p.Arg132Pro (c.395G>C) pathogenic?

DCAF17 p.Arg132Pro (c.395G>C) is classified Uncertain significance in DCAF17 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-29). AlphaMissense: likely pathogenic (0.9841); Very rare (popmax 8.48e-05%, nfe); Associated with Woodhouse-Sakati syndrome.

What condition is associated with DCAF17 p.Arg132Pro (c.395G>C)?

DCAF17 p.Arg132Pro (c.395G>C) is associated with Woodhouse-Sakati syndrome (ClinVar).

How common is DCAF17 p.Arg132Pro (c.395G>C) in the general population?

DCAF17 p.Arg132Pro (c.395G>C) is very rare (popmax 8.48e-05%, nfe) (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.Arg132Pro (c.395G>C)?

AlphaMissense predicts likely pathogenic (score 0.9841) — an in-silico prediction, not a clinical call.

DCAF17 p.Arg132Pro

c.395G>C · rs756053962 · VCV2115601

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9841 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Woodhouse-Sakati syndrome

Computational evidence

Protein change
AlphaMissense	0.9841	likely pathogenic · top 4% in DCAF17
REVEL	0.553	indeterminate
SaProt	LLR -16.85	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 34 kb · p 0.67 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.48e-05% European (non-Finnish) · 1/1,179,360 alleles

Overall 6.84e-05% 1/1,461,156 alleles · very rare

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.Arg132Pro
Coding: c.395G>C
MANE Select: NM_025000
dbSNP: rs756053962
Type: single nucleotide variant
Location: chr2:171448754 (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

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.Arg132Cys Uncertain significance ★★ ⚠ same residue
DCAF17 p.Arg132His 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

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-arg132pro (accessed [today's date]).

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