Is DCAF5 p.Phe733Ser (c.2198T>C) pathogenic?

DCAF5 p.Phe733Ser (c.2198T>C) is classified Uncertain significance in DCAF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: likely benign (0.0669); Very rare (popmax 0.00446%, eas).

How common is DCAF5 p.Phe733Ser (c.2198T>C) in the general population?

DCAF5 p.Phe733Ser (c.2198T>C) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about DCAF5 p.Phe733Ser (c.2198T>C)?

AlphaMissense predicts likely benign (score 0.0669) — an in-silico prediction, not a clinical call.

DCAF5 p.Phe733Ser

c.2198T>C · rs529216482 · VCV2469173

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0669 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0669	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -2.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.1	GERP -3.7, phastCons 0.23
Regional constraint	o/e 0.92	unconstrained · MANE · 1,534 bp · p 0.053 · regional, not allelic
Overall
CADD	12.41	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 0.00446% East Asian · 2/44,880 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000558% 9/1,614,112 alleles · very rare exomes 7/1,461,822 · genomes 2/152,290 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.008%	12,502
East Asiangrpmax	0.00446%	22,440
European (non-Finnish)	0.000169%	590,009

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DCAF5
Protein: p.Phe733Ser
Coding: c.2198T>C
MANE Select: NM_003861
dbSNP: rs529216482
Type: single nucleotide variant
Location: chr14:69054488 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.00 · 2 PDB
Residue 733: the 'disordered' region

Full DCAF5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCAF5 p.Ala189Pro Uncertain significance ★ ⚠ same type
DCAF5 p.Ala250Asp Uncertain significance ★ ⚠ same type
DCAF5 p.Ala405Thr Uncertain significance ★ ⚠ same type
DCAF5 p.Ala526Thr Uncertain significance ★ ⚠ same type
DCAF5 p.Ala647Pro Uncertain significance ★ ⚠ same type
DCAF5 p.Ala800Pro Uncertain significance ★ ⚠ same type
DCAF5 p.Arg291Cys Uncertain significance ★ ⚠ same type
DCAF5 p.Arg375Gln 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/dcaf5-p-phe733ser (accessed [today's date]).

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