Is DCAF17 p.Met1Val (c.1A>G) pathogenic?

DCAF17 p.Met1Val (c.1A>G) is classified Pathogenic/Likely pathogenic in DCAF17 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-02). Ultra-rare (popmax 0.018%, sas); Associated with Woodhouse-Sakati syndrome.

What condition is associated with DCAF17 p.Met1Val (c.1A>G)?

DCAF17 p.Met1Val (c.1A>G) is associated with Woodhouse-Sakati syndrome (ClinVar).

How common is DCAF17 p.Met1Val (c.1A>G) in the general population?

DCAF17 p.Met1Val (c.1A>G) is ultra-rare (popmax 0.018%, sas) (gnomAD).

How is Woodhouse-Sakati syndrome inherited?

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

DCAF17 p.Met1Val

c.1A>G · rs762608997 · VCV2960660

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.018%, sas)

Conditions

Woodhouse-Sakati syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.106	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP -0.65, phastCons 1
Overall
CADD	20.5	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.018% South Asian · 15/83,536 alleles

Filtering AF 0.0111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00891%

Overall 0.00109% 15/1,374,922 alleles · ultra-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.Met1Val
Coding: c.1A>G
MANE Select: NM_025000
dbSNP: rs762608997
Type: single nucleotide variant
Location: chr2:171434578 (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.Met1Leu Pathogenic ★ same residue
DCAF17 p.Met1Thr Pathogenic ★ same residue
DCAF17 c.127-1G>C Pathogenic/Likely pathogenic ★★ same condition
DCAF17 p.Arg194Ter 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-met1val (accessed [today's date]).

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