Is DCAF15 p.Arg306Pro (c.917G>C) pathogenic?

DCAF15 p.Arg306Pro (c.917G>C) is classified Uncertain significance in DCAF15 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-25). AlphaMissense: likely benign (0.0718); Ultra-rare (popmax 0.0427%, afr).

How common is DCAF15 p.Arg306Pro (c.917G>C) in the general population?

DCAF15 p.Arg306Pro (c.917G>C) is ultra-rare (popmax 0.0427%, afr) (gnomAD).

What do computational predictors say about DCAF15 p.Arg306Pro (c.917G>C)?

AlphaMissense predicts likely benign (score 0.0718) — an in-silico prediction, not a clinical call.

DCAF15 p.Arg306Pro

c.917G>C · rs369708095 · VCV2408500

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0718 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0427%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0718	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -4.10	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 0.74	GERP -3.8, phastCons 0.004
Regional constraint	o/e 1.05	unconstrained · MANE · 674 bp · p 0.47 · regional, not allelic
Overall
CADD	1.258	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 0.0427% African / African-American · 32/74,886 alleles

Filtering AF 0.031% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0271%

Overall 0.00198% 32/1,612,396 alleles · ultra-rare exomes 10/1,460,384 · genomes 22/152,012 · 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: DCAF15
Protein: p.Arg306Pro
Coding: c.917G>C
MANE Select: NM_138353
dbSNP: rs369708095
Type: single nucleotide variant
Location: chr19:13959177 (GRCh38)
Gene constraint: LOEUF 0.502 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 78.92 · 9 PDB
Residue 306: the 'disordered' region

Full DCAF15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCAF15 p.Arg306Cys Uncertain significance ★ ⚠ same residue
DCAF15 p.Ile153= Benign ★★ same type
DCAF15 p.Ala149Thr Uncertain significance ★ ⚠ same type
DCAF15 p.Ala149Val Uncertain significance ★ ⚠ same type
DCAF15 p.Ala162Gly Uncertain significance ★ ⚠ same type
DCAF15 p.Ala23Gly Uncertain significance ★ ⚠ same type
DCAF15 p.Ala2Val Uncertain significance ★ ⚠ same type
DCAF15 p.Ala303Val 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/dcaf15-p-arg306pro (accessed [today's date]).

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