Is DCAF5 p.Ala189Pro (c.565G>C) pathogenic?

DCAF5 p.Ala189Pro (c.565G>C) is classified Uncertain significance in DCAF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-18). AlphaMissense: likely pathogenic (0.7895); Absent from gnomAD v4.1.

How common is DCAF5 p.Ala189Pro (c.565G>C) in the general population?

DCAF5 p.Ala189Pro (c.565G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCAF5 p.Ala189Pro (c.565G>C)?

AlphaMissense predicts likely pathogenic (score 0.7895) — an in-silico prediction, not a clinical call.

DCAF5 p.Ala189Pro

c.565G>C · rs2502958918 · VCV2328116

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7895 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7895	likely pathogenic
REVEL	0.375	indeterminate
SaProt	LLR -9.20	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 61 kb · p 6.5e-22 · regional, not allelic
Overall
CADD	23.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DCAF5
Protein: p.Ala189Pro
Coding: c.565G>C
MANE Select: NM_003861
dbSNP: rs2502958918
Type: single nucleotide variant
Location: chr14:69116466 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.00 · 2 PDB

Full DCAF5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCAF5 p.Ala250Asp Uncertain significance ★ ⚠ same type
DCAF5 p.Ala405Thr Uncertain significance ★ ⚠ same type
DCAF5 p.Ala526Thr Uncertain significance ★ ⚠ same type
DCAF5 p.Ala647Pro Uncertain significance ★ ⚠ same type
DCAF5 p.Ala800Pro Uncertain significance ★ ⚠ same type
DCAF5 p.Arg291Cys Uncertain significance ★ ⚠ same type
DCAF5 p.Arg375Gln Uncertain significance ★ ⚠ same type
DCAF5 p.Arg424His Uncertain significance ★ ⚠ same type

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/dcaf5-p-ala189pro (accessed [today's date]).

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