Is DCAF17 p.Val27Met (c.79G>A) pathogenic?

DCAF17 p.Val27Met (c.79G>A) is classified Uncertain significance in DCAF17 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-08). AlphaMissense: likely benign (0.1069); Very rare (popmax 0.00421%, afr); Associated with Woodhouse-Sakati syndrome.

What condition is associated with DCAF17 p.Val27Met (c.79G>A)?

DCAF17 p.Val27Met (c.79G>A) is associated with Woodhouse-Sakati syndrome (ClinVar).

How common is DCAF17 p.Val27Met (c.79G>A) in the general population?

DCAF17 p.Val27Met (c.79G>A) is very rare (popmax 0.00421%, afr) (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.Val27Met (c.79G>A)?

AlphaMissense predicts likely benign (score 0.1069) — an in-silico prediction, not a clinical call.

DCAF17 p.Val27Met

c.79G>A · VCV3672813

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1069 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00421%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Woodhouse-Sakati syndrome

Computational evidence

Protein change
AlphaMissense	0.1069	likely benign
REVEL	0.013	strongly benign-leaning
SaProt	LLR -8.01	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 6.4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 34 kb · p 0.67 · regional, not allelic
Overall
CADD	25.4	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 0.00421% African / African-American · 3/71,206 alleles

Filtering AF 0.00112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00061%

Overall 0.000261% 4/1,535,304 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00421%	23,735
South Asian	0.00119%	84,060

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.Val27Met
Coding: c.79G>A
MANE Select: NM_025000
Type: single nucleotide variant
Location: chr2:171434656 (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.Val27Gly Uncertain significance ★★ ⚠ same residue
DCAF17 p.Val27= Likely benign ★ 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-val27met (accessed [today's date]).

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