Is DCAF15 p.Gln467Glu (c.1399C>G) pathogenic?

DCAF15 p.Gln467Glu (c.1399C>G) is classified Uncertain significance in DCAF15 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-20). AlphaMissense: likely benign (0.2412); Very rare (popmax 0.00504%, amr).

How common is DCAF15 p.Gln467Glu (c.1399C>G) in the general population?

DCAF15 p.Gln467Glu (c.1399C>G) is very rare (popmax 0.00504%, amr) (gnomAD).

What do computational predictors say about DCAF15 p.Gln467Glu (c.1399C>G)?

AlphaMissense predicts likely benign (score 0.2412) — an in-silico prediction, not a clinical call.

DCAF15 p.Gln467Glu

c.1399C>G · VCV3838411

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2412 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00504%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2412	likely benign
REVEL	0.54	indeterminate
SaProt	LLR -9.17	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 1,211 bp · p 1.1e-10 · regional, not allelic
Overall
CADD	25.0	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 0.00504% Admixed American · 3/59,490 alleles

Filtering AF 0.00134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000671%

Overall 0.000551% 8/1,452,058 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00504%	19,830
Remaining individualsnot grpmax-eligible	0.00162%	61,600
European (non-Finnish)	0.000341%	293,337

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.Gln467Glu
Coding: c.1399C>G
MANE Select: NM_138353
Type: single nucleotide variant
Location: chr19:13959854 (GRCh38)
Gene constraint: LOEUF 0.502 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 78.92 · 9 PDB
Residue 467: a turn

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

Similar variants

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
DCAF15 p.Ala305Gly 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-gln467glu (accessed [today's date]).

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