Is DCAF15 p.Ser7Pro (c.19T>C) pathogenic?

DCAF15 p.Ser7Pro (c.19T>C) is classified Uncertain significance in DCAF15 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: ambiguous (0.4251); Absent from gnomAD v4.1.

How common is DCAF15 p.Ser7Pro (c.19T>C) in the general population?

DCAF15 p.Ser7Pro (c.19T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCAF15 p.Ser7Pro (c.19T>C)?

AlphaMissense predicts ambiguous (score 0.4251) — an in-silico prediction, not a clinical call.

DCAF15 p.Ser7Pro

c.19T>C · VCV4836233

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4251 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4251	ambiguous
REVEL	0.133	moderately benign-leaning
SaProt	LLR -5.78	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 7.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 6,592 bp · p 1.2e-09 · regional, not allelic
Overall
CADD	27.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DCAF15
Protein: p.Ser7Pro
Coding: c.19T>C
MANE Select: NM_138353
Type: single nucleotide variant
Location: chr19:13952531 (GRCh38)
Gene constraint: LOEUF 0.502 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 78.92 · 9 PDB
Residue 7: the 'disordered' region

Full DCAF15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCAF15 p.Ser7Trp Uncertain significance ★ ⚠ same residue
DCAF15 p.Ile153= Benign ★★ same type
DCAF15 p.Ala149Thr Uncertain significance ★ ⚠ same type
DCAF15 p.Ala149Val Uncertain significance ★ ⚠ same type
DCAF15 p.Ala162Gly Uncertain significance ★ ⚠ same type
DCAF15 p.Ala23Gly Uncertain significance ★ ⚠ same type
DCAF15 p.Ala2Val Uncertain significance ★ ⚠ same type
DCAF15 p.Ala303Val 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/dcaf15-p-ser7pro (accessed [today's date]).

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