Is DCAF13 p.Arg408His (c.1223G>A) pathogenic?

DCAF13 p.Arg408His (c.1223G>A) is classified Uncertain significance in DCAF13 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-10). AlphaMissense: likely benign (0.0867); Ultra-rare (popmax 0.0305%, amr).

How common is DCAF13 p.Arg408His (c.1223G>A) in the general population?

DCAF13 p.Arg408His (c.1223G>A) is ultra-rare (popmax 0.0305%, amr) (gnomAD).

What do computational predictors say about DCAF13 p.Arg408His (c.1223G>A)?

AlphaMissense predicts likely benign (score 0.0867) — an in-silico prediction, not a clinical call.

DCAF13 p.Arg408His

c.1223G>A · VCV3270960

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0867 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0305%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0867	likely benign
REVEL	0.449	indeterminate
SaProt	LLR -11.81	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 1,377 bp · p 0.39 · regional, not allelic
Overall
CADD	23.8	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

Grpmax group 0.0305% Admixed American · 18/59,020 alleles

Filtering AF 0.0197% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0162%

Overall 0.00652% 105/1,610,818 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0305%	3,279
Remaining individualsnot grpmax-eligible	0.0128%	7,798
South Asian	0.00666%	15,025
European (non-Finnish)	0.00577%	17,341
African / African-American	0.00401%	24,915
Finnishnot grpmax-eligible	0.00313%	31,980

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: DCAF13
Protein: p.Arg408His
Coding: c.1223G>A
MANE Select: NM_015420
Type: single nucleotide variant
Location: chr8:103441591 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.84 · 3 PDB
Residue 408: an α-helix; the 'required for nucleolar location' region

Full DCAF13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCAF13 p.His327Arg Uncertain significance ★★ ⚠ same type
DCAF13 p.Phe381Cys Uncertain significance ★★ ⚠ same type
DCAF13 p.Ala109Gly Benign ★★ same type
DCAF13 p.Ala70= Benign ★★ same type
DCAF13 c.-20C>T Uncertain significance ★ same type
DCAF13 c.-30T>C Uncertain significance ★ same type
DCAF13 c.-33A>G Uncertain significance ★ same type
DCAF13 c.-38C>A 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/dcaf13-p-arg408his (accessed [today's date]).

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