Is DCAF4L2 p.Val366Ala (c.1097T>C) pathogenic?

DCAF4L2 p.Val366Ala (c.1097T>C) is classified Uncertain significance in DCAF4L2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-25). AlphaMissense: ambiguous (0.492); Absent from gnomAD v4.1.

How common is DCAF4L2 p.Val366Ala (c.1097T>C) in the general population?

DCAF4L2 p.Val366Ala (c.1097T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCAF4L2 p.Val366Ala (c.1097T>C)?

AlphaMissense predicts ambiguous (score 0.492) — an in-silico prediction, not a clinical call.

DCAF4L2 p.Val366Ala

c.1097T>C · VCV3270983

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.492 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.492	ambiguous
REVEL	0.298	indeterminate
SaProt	LLR -9.11	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.7, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 1,184 bp · p 0.68 · regional, not allelic
Overall
CADD	24.2	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: DCAF4L2
Protein: p.Val366Ala
Coding: c.1097T>C
MANE Select: NM_152418
Type: single nucleotide variant
Location: chr8:87872875 (GRCh38)
Gene constraint: LOEUF 1.096 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.17

Full DCAF4L2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCAF4L2 p.Ala12Val Uncertain significance ★ ⚠ same type
DCAF4L2 p.Ala185Ser Uncertain significance ★ ⚠ same type
DCAF4L2 p.Ala25Val Uncertain significance ★ ⚠ same type
DCAF4L2 p.Ala367Thr Uncertain significance ★ ⚠ same type
DCAF4L2 p.Arg254His Uncertain significance ★ ⚠ same type
DCAF4L2 p.Arg30Gln Uncertain significance ★ ⚠ same type
DCAF4L2 p.Arg371Cys Uncertain significance ★ ⚠ same type
DCAF4L2 p.Arg50His 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/dcaf4l2-p-val366ala (accessed [today's date]).

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