Is DCAF17 p.Pro58Ser (c.172C>T) pathogenic?

DCAF17 p.Pro58Ser (c.172C>T) is classified Uncertain significance in DCAF17 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-25). AlphaMissense: ambiguous (0.4297); Very rare (popmax 0.00133%, afr).

How common is DCAF17 p.Pro58Ser (c.172C>T) in the general population?

DCAF17 p.Pro58Ser (c.172C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about DCAF17 p.Pro58Ser (c.172C>T)?

AlphaMissense predicts ambiguous (score 0.4297) — an in-silico prediction, not a clinical call.

DCAF17 p.Pro58Ser

c.172C>T · VCV4957736

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4297 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4297	ambiguous
REVEL	0.12	moderately benign-leaning
SaProt	LLR -5.82	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 34 kb · p 0.67 · regional, not allelic
Overall
CADD	24.7	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 0.00133% African / African-American · 1/75,010 alleles

Overall 6.84e-05% 1/1,461,372 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: DCAF17
Protein: p.Pro58Ser
Coding: c.172C>T
MANE Select: NM_025000
Type: single nucleotide variant
Location: chr2:171435128 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.38

Full DCAF17 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCAF17 p.Pro58= Likely benign ★★ same residue
DCAF17 c.127-1G>C Pathogenic/Likely pathogenic ★★ same type
DCAF17 p.Arg194Ter Pathogenic/Likely pathogenic ★★ same type
DCAF17 p.Met1Val Pathogenic/Likely pathogenic ★★ same type
DCAF17 p.Trp129Ter Pathogenic ★★ same type
DCAF17 p.Trp302Ter Pathogenic ★★ same type
DCAF17 c.1266+4T>C Uncertain significance ★★ same type
DCAF17 c.*126A>T 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/dcaf17-p-pro58ser (accessed [today's date]).

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