Is DCAF16 p.Arg96Ser (c.288A>C) pathogenic?

DCAF16 p.Arg96Ser (c.288A>C) is classified Uncertain significance in DCAF16 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-01). AlphaMissense: likely pathogenic (0.8265); Very rare (popmax 0.00246%, nfe).

How common is DCAF16 p.Arg96Ser (c.288A>C) in the general population?

DCAF16 p.Arg96Ser (c.288A>C) is very rare (popmax 0.00246%, nfe) (gnomAD).

What do computational predictors say about DCAF16 p.Arg96Ser (c.288A>C)?

AlphaMissense predicts likely pathogenic (score 0.8265) — an in-silico prediction, not a clinical call.

DCAF16 p.Arg96Ser

c.288A>C · VCV3270974

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8265 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00246%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8265	likely pathogenic · top 7% in DCAF16
REVEL	0.283	benign-leaning
SaProt	LLR -5.83	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.7	GERP 0.72, phastCons 0.018
Regional constraint	o/e 1.01	unconstrained · MANE · 647 bp · p 0.93 · regional, not allelic
Overall
CADD	16.53	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 0.00246% European (non-Finnish) · 29/1,179,988 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.0018% 29/1,613,736 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.Arg96Ser
Coding: c.288A>C
MANE Select: NM_017741
Type: single nucleotide variant
Location: chr4:17803854 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 38.26 · 3 PDB

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.Asn171Ser Uncertain significance ★ ⚠ same type
DCAF16 p.Asp137Glu Uncertain significance ★ ⚠ same type
DCAF16 p.Asp9Val Uncertain significance ★ ⚠ same type
DCAF16 p.Glu27Asp 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-arg96ser (accessed [today's date]).

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