Is DCAF4 p.Ser55Phe (c.164C>T) pathogenic?

DCAF4 p.Ser55Phe (c.164C>T) is classified Uncertain significance in DCAF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-16). AlphaMissense: likely benign (0.1481); Ultra-rare (popmax 0.0227%, afr).

How common is DCAF4 p.Ser55Phe (c.164C>T) in the general population?

DCAF4 p.Ser55Phe (c.164C>T) is ultra-rare (popmax 0.0227%, afr) (gnomAD).

What do computational predictors say about DCAF4 p.Ser55Phe (c.164C>T)?

AlphaMissense predicts likely benign (score 0.1481) — an in-silico prediction, not a clinical call.

DCAF4 p.Ser55Phe

c.164C>T · VCV4237857

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1481 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1481	likely benign
REVEL	0.274	benign-leaning
SaProt	LLR -9.72	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.3	GERP 2.4, phastCons 0.76
Regional constraint	o/e 0.89	unconstrained · MANE · 21 kb · p 0.0042 · regional, not allelic
Overall
CADD	22.9	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 0.0227% African / African-American · 17/74,980 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0118%

Overall 0.00137% 22/1,611,070 alleles · ultra-rare exomes 14/1,458,702 · genomes 8/152,368 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0227%	4,411
Admixed American	0.00335%	29,889
Remaining individualsnot grpmax-eligible	0.00321%	31,181
Finnishnot grpmax-eligible	0.00157%	63,770

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.Ser55Phe
Coding: c.164C>T
MANE Select: NM_015604
Type: single nucleotide variant
Location: chr14:72939873 (GRCh38)
Gene constraint: LOEUF 0.787 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.34 · 1 PDB
Residue 55: the 'disordered' region

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

Similar variants

DCAF4 p.Ser28= Benign ★★ same type
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

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-ser55phe (accessed [today's date]).

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