Is DCAF4 p.Ser28= (c.84T>C) pathogenic?

DCAF4 p.Ser28= (c.84T>C) is classified Benign in DCAF4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-04-24). Common (popmax 5.87%, afr) — too common for a highly-penetrant pathogenic allele.

DCAF4 p.Ser28=

Q: How common is DCAF4 p.Ser28= (c.84T>C) in the general population?

DCAF4 p.Ser28= (c.84T>C) is common (popmax 5.87%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.84T>C · rs17122598 · VCV768661

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.87%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.98	GERP -4.4
Overall
CADD	1.667	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.87% African / African-American · 4,363/74,362 alleles

Filtering AF 5.72% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.66%

Overall 0.361% 5,805/1,606,600 alleles · common exomes 3,169/1,454,252 · genomes 2,636/152,348 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.87%	17
Ashkenazi Jewishnot grpmax-eligible	1.91%	52
Remaining individualsnot grpmax-eligible	0.581%	172
Admixed American	0.463%	216
Middle Eastern	0.434%	230
South Asian	0.0189%	5,288
European (non-Finnish)	0.0182%	5,504

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: DCAF4
Protein: p.Ser28=
Coding: c.84T>C
MANE Select: NM_015604
dbSNP: rs17122598
Type: single nucleotide variant
Location: chr14:72938062 (GRCh38)
Gene constraint: LOEUF 0.787 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.34 · 1 PDB
Residue 28: the 'disordered' region

Full DCAF4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCAF4 p.Ser325Gly Likely benign ★★ same type
DCAF4 p.Ala125Val Uncertain significance ★ ⚠ same type
DCAF4 p.Ala168Gly Uncertain significance ★ ⚠ same type
DCAF4 p.Ala179Thr Uncertain significance ★ ⚠ same type
DCAF4 p.Ala233Val Uncertain significance ★ ⚠ same type
DCAF4 p.Ala285Ser Uncertain significance ★ ⚠ same type
DCAF4 p.Ala461Thr Uncertain significance ★ ⚠ same type
DCAF4 p.Ala478Thr 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/dcaf4-p-ser28 (accessed [today's date]).

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