Is DCAF17 p.Val75Ala (c.224T>C) pathogenic?

DCAF17 p.Val75Ala (c.224T>C) is classified Uncertain significance in DCAF17 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-22). AlphaMissense: ambiguous (0.4918); Very rare (popmax 0.000255%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DCAF17 p.Val75Ala (c.224T>C)?

DCAF17 p.Val75Ala (c.224T>C) is associated with Inborn genetic diseases (ClinVar).

How common is DCAF17 p.Val75Ala (c.224T>C) in the general population?

DCAF17 p.Val75Ala (c.224T>C) is very rare (popmax 0.000255%, nfe) (gnomAD).

What do computational predictors say about DCAF17 p.Val75Ala (c.224T>C)?

AlphaMissense predicts ambiguous (score 0.4918) — an in-silico prediction, not a clinical call.

DCAF17 p.Val75Ala

c.224T>C · VCV3838414

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4918 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000255%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4918	ambiguous
REVEL	0.066	moderately benign-leaning
SaProt	LLR -10.62	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 34 kb · p 0.67 · regional, not allelic
Overall
CADD	24.9	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 0.000255% European (non-Finnish) · 3/1,177,828 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,611,530 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.Val75Ala
Coding: c.224T>C
MANE Select: NM_025000
Type: single nucleotide variant
Location: chr2:171435180 (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

Similar variants

DCAF17 p.Val75Leu Uncertain significance ★ ⚠ same residue
DCAF17 p.Ala440Thr Uncertain significance ★★ ⚠ same condition
DCAF17 p.Asn70Asp Uncertain significance ★★ ⚠ same condition
DCAF17 p.Asn70Ser Uncertain significance ★★ ⚠ same condition
DCAF17 p.Glu142Lys Uncertain significance ★★ ⚠ same condition
DCAF17 p.Ile122Leu Uncertain significance ★★ ⚠ same condition
DCAF17 p.Ile305Val Uncertain significance ★★ ⚠ same condition
DCAF17 p.Lys46Ile 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-val75ala (accessed [today's date]).

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