Is DCAF5 p.Ala800Pro (c.2398G>C) pathogenic?

DCAF5 p.Ala800Pro (c.2398G>C) is classified Uncertain significance in DCAF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely benign (0.0668); Very rare (popmax 0.00534%, afr).

How common is DCAF5 p.Ala800Pro (c.2398G>C) in the general population?

DCAF5 p.Ala800Pro (c.2398G>C) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about DCAF5 p.Ala800Pro (c.2398G>C)?

AlphaMissense predicts likely benign (score 0.0668) — an in-silico prediction, not a clinical call.

DCAF5 p.Ala800Pro

c.2398G>C · VCV4658643

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0668 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0668	likely benign
REVEL	0.045	moderately benign-leaning
SaProt	LLR -5.48	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 0.88	GERP -2.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 1,534 bp · p 0.053 · regional, not allelic
Overall
CADD	15.33	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 0.00534% African / African-American · 4/74,930 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000248% 4/1,614,086 alleles · very rare exomes 0/1,461,882 · genomes 4/152,204 · joint denominator

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: DCAF5
Protein: p.Ala800Pro
Coding: c.2398G>C
MANE Select: NM_003861
Type: single nucleotide variant
Location: chr14:69054288 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.00 · 2 PDB
Residue 800: the 'disordered' region

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

Similar variants

DCAF5 p.Ala189Pro Uncertain significance ★ ⚠ same type
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.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-ala800pro (accessed [today's date]).

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