Is DCAF16 p.His138Arg (c.413A>G) pathogenic?

DCAF16 p.His138Arg (c.413A>G) is classified Uncertain significance in DCAF16 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-27). AlphaMissense: likely benign (0.1921); Very rare (popmax 0.00167%, amr).

How common is DCAF16 p.His138Arg (c.413A>G) in the general population?

DCAF16 p.His138Arg (c.413A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DCAF16 p.His138Arg (c.413A>G)?

AlphaMissense predicts likely benign (score 0.1921) — an in-silico prediction, not a clinical call.

DCAF16 p.His138Arg

c.413A>G · VCV3838413

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1921 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1921	likely benign
REVEL	0.107	moderately benign-leaning
SaProt	LLR -5.23	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 1.8	GERP -0.49, phastCons 0.82
Regional constraint	o/e 1.01	unconstrained · MANE · 647 bp · p 0.93 · regional, not allelic
Overall
CADD	15.42	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 0.00167% Admixed American · 1/60,016 alleles

Overall 6.84e-05% 1/1,461,894 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: DCAF16
Protein: p.His138Arg
Coding: c.413A>G
MANE Select: NM_017741
Type: single nucleotide variant
Location: chr4:17803729 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 38.26 · 3 PDB
Residue 138: an α-helix

Full DCAF16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCAF16 p.Ala144Thr Uncertain significance ★ ⚠ same type
DCAF16 p.Ala78Thr Uncertain significance ★ ⚠ same type
DCAF16 p.Arg191His Uncertain significance ★ ⚠ same type
DCAF16 p.Arg91Gln Uncertain significance ★ ⚠ same type
DCAF16 p.Arg96Ser Uncertain significance ★ ⚠ same type
DCAF16 p.Asn171Ser Uncertain significance ★ ⚠ same type
DCAF16 p.Asp137Glu Uncertain significance ★ ⚠ same type
DCAF16 p.Asp9Val 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/dcaf16-p-his138arg (accessed [today's date]).

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