Is DCAF8 p.Arg352Gln (c.1055G>A) pathogenic?

DCAF8 p.Arg352Gln (c.1055G>A) is classified Uncertain significance in DCAF8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-30). AlphaMissense: likely pathogenic (0.8102); Very rare (popmax 0.00134%, afr).

How common is DCAF8 p.Arg352Gln (c.1055G>A) in the general population?

DCAF8 p.Arg352Gln (c.1055G>A) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about DCAF8 p.Arg352Gln (c.1055G>A)?

AlphaMissense predicts likely pathogenic (score 0.8102) — an in-silico prediction, not a clinical call.

DCAF8 p.Arg352Gln

c.1055G>A · VCV3271006

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8102 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8102	likely pathogenic
REVEL	0.519	indeterminate
SaProt	LLR -6.13	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.53	unconstrained · MANE · 15 kb · p 9.7e-17 · regional, not allelic
Overall
CADD	24.4	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 0.00134% African / African-American · 1/74,906 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000806% 13/1,613,474 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,906
South Asian	0.0011%	91,076
European (non-Finnish)	0.000933%	107,230

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: DCAF8
Protein: p.Arg352Gln
Coding: c.1055G>A
MANE Select: NM_015726
Type: single nucleotide variant
Location: chr1:160231312 (GRCh38)
Gene constraint: LOEUF 0.466 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.60 · 2 PDB

Full DCAF8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCAF8 p.Arg117Cys Uncertain significance ★★ ⚠ same type
DCAF8 p.Arg122Trp Uncertain significance ★★ ⚠ same type
DCAF8 p.Asn343Ser Uncertain significance ★★ ⚠ same type
DCAF8 p.Ser419Asn Uncertain significance ★★ ⚠ same type
DCAF8 p.Ser576Pro Uncertain significance ★★ ⚠ same type
DCAF8 p.Arg204= Benign/Likely benign ★★ same type
DCAF8 p.Arg263= Benign ★★ same type
DCAF8 p.Asp214= Likely benign ★★ 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/dcaf8-p-arg352gln (accessed [today's date]).

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